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1.
Anticancer Res ; 39(9): 4957-4963, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519601

RESUMO

BACKGROUND/AIM: Adjuvant radiotherapy (RT) damages multiple layers of skin, muscle, blood vessels and blood cells that are included within the RT area. Indirect, bystander systemic effects could also develop in cells not directly hit by radiation. MATERIALS AND METHODS: Ninety-three female patients recovering from breast cancer surgery and 82 female healthy blood donors were analyzed. For identification of systemic adaptive and innate immune response, rapid and low-cost blood-based biomarkers were assayed. RESULTS: Post-operated breast cancer patients had a decreased number of circulating adaptive immune response cells but increased number of circulating immunosuppressive myeloid subpopulations. RT decreased the number of T-cells and platelets without influencing the number of immunosuppressive myeloid subpopulations. Alterations in the number and phenotypes of T-cell subpopulations were associated with SNPs. CONCLUSION: The combination of RT and immunotherapy might provide optimal treatment for cancer patients.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Imunidade Celular/genética , Imunidade Celular/efeitos da radiação , Contagem de Leucócitos , Fenótipo , Polimorfismo de Nucleotídeo Único , Imunidade Adaptativa , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Estudos de Casos e Controles , Feminino , Humanos , Imunidade Inata , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Radioterapia Adjuvante , Linfócitos T/imunologia , Linfócitos T/metabolismo
2.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(6): 684-688, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31315723

RESUMO

OBJECTIVE: To analyze the characteristics of cellular immune function and its prognostic risk factors in patients with community-acquired pneumonia (CAP). METHODS: The clinical data of patients diagnosed as CAP admitted to department of respiratory and critical care medicine of the Second Affiliated Hospital of Anhui Medical University from June 2018 to February 2019 were retrospectively analyzed. The patients were divided into survival group and death group according to the mortality at discharge and 28-day survival after hospital discharge; in addition, they were divided into bacterial group, fungi group and mixed infection group according to pathogen results at discharge. The differences of general clinical characteristics, arterial blood gas analysis indexes, plasma albumin, cellular immune function, inflammatory cytokines, the length of hospital stay among groups were analyzed. The correlation between the prognosis-related indicators in patients were analyzed by Pearson test or Spearman test, and Logistic regression model was used to analyze the risk factors of patients in non-survival group. RESULTS: 106 patients were finally enrolled, 69 of whom were survived, and 37 dead. Among 56 patients with pathogen results, 27 were diagnosed as bacterial infection, 11 as fungal infection, and 18 with mixed infection. Compared with the survival group, plasma albumin level, total T cell count, CD4+T cell count, CD8+T cell count were decreased in the death group, temperature, pH, acute physiology and chronic health evaluation II (APACHE II), procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein (CRP) were increased, and the length of hospital stay was significantly shortened. While there was no significant difference in gender, age, mean arterial pressure, arterial oxygen pressure, CD4+/CD8+, regulation T cell/effect T cell (TREG/TEF) between the two groups. Correlation analysis showed that plasma albumin, the length of hospital stay, APACHE II score, CD4+T cell count, CD8+T cell count, CD4+/CD8+, PCT, IL-6, CRP were correlated with death (r value was -0.480, -0.209, 0.203, -0.279, -0.270, 0.271, 0.247, 0.410, 0.329, all P < 0.05). Logistic regression analysis showed that plasma albumin, CD4+T cell count, CD8+T cell count, CD4+/CD8+decreased; APACHE II score, PCT, IL-6, and CRP increased; the length of hospital stay were correlated with death, and all were independent risk factors for death in CAP patients (all P < 0.05). Correlation analysis showed that the APACHE II score was negatively related to plasma albumin (r = -0.375, P < 0.05), positively related to CRP and IL-6 (r value was 0.363 and 0.333 respectively, both P < 0.05); negative correlation between plasma albumin and IL-6 (r = -0.372, P < 0.05), PCT and CD4+T cell count (r = -0.354, P < 0.05), CRP and the length of hospital stay (r = -0.356, P < 0.05). There were no significant correlations between the others. There was no significant difference in cellular immune function or inflammatory factor expression between different pathogenic infections. CONCLUSIONS: Cellular immune dysfunction, hypoproteinemia, APACHE II score and elevated inflammatory index are all influential factors for the death of CAP patients. Apart from conventional anti-infective treatment, the symptoms of hypoproteinemia and cellular immune function can predict the severity and prognosis of CAP patients.


Assuntos
Infecções Comunitárias Adquiridas/imunologia , Imunidade Celular/fisiologia , Pneumonia/imunologia , APACHE , Humanos , Prognóstico , Estudos Retrospectivos , Fatores de Risco
3.
Int J Nanomedicine ; 14: 4867-4880, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308663

RESUMO

Background: The demand for an effective vaccine delivery system that drives a suitable immune response is increasing. The oxidized carbon nanosphere (OCN), a negatively charged carbon nanoparticle, has the potential to fulfill this requirement because it can efficiently deliver macromolecules into cells and allows endosomal leakage. However, fundamental insights into how OCNs are taken up by antigen-presenting cells, and the intracellular behavior of delivered molecules is lacking. Furthermore, how immune responses are stimulated by OCN-mediated delivery has not been investigated. Purpose: In this study, the model protein antigen ovalbumin (OVA) was used to investigate the uptake mechanism and intracellular fate of OCN-mediated delivery of protein in macrophages. Moreover, the immune response triggered by OVA delivered by OCNs was characterized. Methods: Bone-marrow-derived macrophages (BMDMs) from mice were used to study antigen uptake and intracellular trafficking. Mice were immunized using OCN-OVA combined with known adjuvants, and the specific immune response was measured. Results: OCNs showed no cytotoxicity against BMDMs. OCN-mediated delivery of OVA into BMDMs was partially temperature independent process. Using specific inhibitors, it was revealed that intracellular delivery of OCN-OVA does not rely on phagocytosis or the clathrin- and lipid raft/caveolae-mediated pathways. Delivered OVA was found to colocalize with compartments containing MHC class I, but not with early endosomes, lysosomes, and autophagosomes. Immunization of OVA using OCNs in combination with the known adjuvant monophosphoryl lipid A specifically enhanced interferon gamma (IFNγ)- and granzyme B-producing cytotoxic T cells (CTLs). Conclusion: OCNs effectively delivered protein antigens into macrophages that localized with compartments containing MHC class I partially by the temperature independent, but not clathrin- and lipid raft/caveolae-mediated pathways. Increased CD8+ T-cell activity was induced by OCN-delivered antigens, suggesting antigen processing toward antigen presentation for CTLs. Taken together, OCNs are a potential protein antigen delivery system that stimulates the cell-mediated immune response.


Assuntos
Antígenos/administração & dosagem , Carbono/química , Sistemas de Liberação de Medicamentos , Imunidade Celular , Nanopartículas/química , Adjuvantes Imunológicos/farmacologia , Animais , Antígenos/imunologia , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Linhagem Celular , Endocitose/efeitos dos fármacos , Endossomos/efeitos dos fármacos , Endossomos/metabolismo , Feminino , Imunidade Celular/efeitos dos fármacos , Cinética , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Nanopartículas/toxicidade , Oxirredução , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia
4.
Parasit Vectors ; 12(1): 347, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300007

RESUMO

BACKGROUND: Live anticoccidial vaccines have been a tremendous success for disease prevention. The establishment of the reverse genetic manipulation platform has enabled the development of Eimeria parasites, the live anticoccidial vaccine strains, as vaccine vectors. In our previous study, recombinant E. tenella expressing a single immunodominant antigen of E. maxima (Et-EmIMP1) was able to protect chickens against challenge infection with E. maxima. This promising result encouraged us to further explore strategies to improve the protection efficacy of recombinant Eimeria and develop it as a vaccine vector. RESULTS: We constructed a novel recombinant Eimeria line expressing apical membrane antigen 1 of E. maxima (Et-EmAMA1) and then immunized chickens with Et-EmAMA1 and/or Et-EmIMP1. We found that the E. maxima soluble antigen-specific cell-mediated immunity was much stronger in the birds that were co-immunized with Et-EmAMA1 and Et-EmIMP1 than in those that were immunized with Et-EmAMA1 or Et-EmIMP1 alone. The oocyst production after E. maxima infection was significantly reduced in the recombinant Eimeria-immunized birds compared with the wild-type-immunized and naïve birds. The oocyst production in the birds co-immunized with Et-EmAMA1 and Et-EmIMP1 was consistently the lowest among the treatment groups after E. maxima infection. CONCLUSIONS: These results demonstrated that Eimeria is an effective vaccine vector that can carry and deliver heterologous Eimeria antigens to the host immune system and trigger specific immune responses. Our results also suggested that increasing the number of recombinant Eimeria lines is an effective approach to enhance protective immunity against infections with heterologous pathogens.


Assuntos
Coccidiose/veterinária , Eimeria tenella/genética , Eimeria/genética , Imunidade Celular , Doenças das Aves Domésticas/prevenção & controle , Vacinas Protozoárias/imunologia , Animais , Antígenos de Protozoários/imunologia , Galinhas , Coccidiose/prevenção & controle , Eimeria/imunologia , Eimeria tenella/imunologia , Doenças das Aves Domésticas/imunologia , Organismos Livres de Patógenos Específicos , Vacinas Atenuadas , Vacinas Sintéticas
5.
Exp Parasitol ; 204: 107725, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31306646

RESUMO

Characterisation of the cellular immune response to schistosomiasis is well established for Schistosoma mansoni but a comprehensive description of T cell-mediated immune responses against S. japonicum infection is lacking. Accordingly, 20 CBA mice were infected with cercariae of S. japonicum and the immune response at different time points was determined. Mouse spleen and liver lymphocytes were isolated from the mice and stimulated with schistosomal adult worm antigen preparation (SWAP) and schistosomal soluble egg antigen (SEA). There was a relatively higher Th1 immune response to SWAP compared to SEA at the early phase of infection (up to week 5 post challenge). However, a Th2 immune response directed against SEA was dominant at week 6 post-infection, a time point when the highest IgG response against both SWAP and, especially, SEA was generated. The regulatory immune response was highest at the early phase of the immune response (up to week 5 post challenge) followed by a rapid decline at week 6-post infection. Before egg-laying, S. japonicum induced a regulatory T cell immune response which may limit the early Th1-mediated immune response that is believed to be protective in murine schistosomiasis. Following egg laying, the immune response was polarized to a Th2 immune response mainly directed against the eggs and this may contribute to parasite survival.


Assuntos
Imunidade Celular , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologia , Linfócitos T/imunologia , Animais , Antígenos de Helmintos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Interleucina-17/imunologia , Interleucina-17/metabolismo , Fígado/citologia , Fígado/imunologia , Fígado/parasitologia , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos CBA , Óvulo/imunologia , Contagem de Ovos de Parasitas , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Caramujos/parasitologia , Baço/citologia , Baço/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th2/imunologia
6.
Biomed Environ Sci ; 32(6): 427-437, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31262388

RESUMO

OBJECTIVE: This study aimed to characterize the diagnostic and vaccine potential of a novel Mycobacterium tuberculosis antigen Rv0674. METHODS: To evaluate the diagnostic potential and antigenicity of Rv0674, IgG was evaluated using ELISA and interferon (IFN)-γ was done by using ELISpot assay among TB patients and healthy donors. For immunogenicity evaluation, BALB/c mice were immunized with Rv0674. Cytokine production was determined by cytokine release assay using an ELISA kit, and the antibodies were tested using ELISA. RESULTS: The results of serum Elisa tests showed that Rv0674 specific immunoglobulin G (IgG) response was higher in TB patients than negative controls. And Rv0674 had good performance in serological test with sensitivity and specificity of 77.1% and 81.1%, respectively. While it shows poor sensitivity and specificity of 26.23% and 79.69% for IFN-γ tests. In BALB/c mice, Rv0674 adjuvant by DDA/Poly I:C could also induce a high level of IFN-γ, interleukin-2 and interleukin-6 as well as a high IgG titer in both high- and low-dose groups indicating that Rv0674 is essential in humoral and cellular immunity. Moreover, the cytokine profile and IgG isotype characterized Rv0674 as a Th1/Th2-mixed-type protective immunity with the predominance of Th1 cytokines. CONCLUSION: Rv0674 may be a good potential candidate for the development of TB serological diagnosis and a new TB vaccine.


Assuntos
Antígenos de Bactérias/imunologia , Tuberculose/imunologia , Adulto , Idoso , Animais , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Tuberculose/diagnóstico , Adulto Jovem
7.
Cancer Immunol Immunother ; 68(8): 1273-1286, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31243491

RESUMO

Therapeutic cancer vaccines have met limited clinical success. In the setting of cancer, the immune system is either tolerized and/or has a limited tumor-specific T cell repertoire. In this study, we explore whether intratumoral (IT) vaccination with an HPV vaccine can elicit quantitative and qualitative differences in immune response as compared to intramuscular (IM) vaccination to overcome immune resistance in established tumors. We report that IT administration of an HPV-16 E7 peptide vaccine formulated with polyinosinic-polycytidylic acid [poly(I:C)] generated an enhanced antitumor effect relative to IM delivery. The elicited anti-tumor effect with IT vaccination was consistent among the vaccinated groups and across various C57BL/6 substrains. IT vaccination resulted in an increased frequency of PD-1hi TILs, which represented both vaccine-targeted and non-vaccine-targeted tumor-specific CD8+ T cells. Overall, the CD8+/Treg ratio was increased within the tumor microenvironment using IT vaccination. We also assessed transcriptional changes in several immune-related genes in the tumor microenvironment of the various treated groups, and our data suggest that IT vaccination leads to upregulation of a broad complement of immunomodulatory genes, including upregulation of interferon gamma (IFNγ) and antigen presentation and processing machine (APM) components. IT vaccine delivery is superior to traditional IM vaccination routes with the potential to improve tumor immunogenicity, which has potential clinical application in the setting of accessible lesions such as head and neck squamous cell carcinomas (HNSCCs).


Assuntos
Linfócitos T CD8-Positivos/imunologia , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Experimentais/imunologia , Proteínas E7 de Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Linfócitos T Reguladores/imunologia , Animais , Apresentação do Antígeno/genética , Vacinas Anticâncer/imunologia , Carcinoma de Células Escamosas/imunologia , Células Cultivadas , Citotoxicidade Imunológica , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/imunologia , Humanos , Imunidade Celular/genética , Injeções Intramusculares , Interferon gama/genética , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Poli I-C/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Vacinação
8.
Acta Virol ; 63(2): 203-210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31230449

RESUMO

The nasal-associated lymphoid tissues (NALTs), embedded in the submucosa of murine upper respiratory tract, represents an important site of induction for local mucosal immune responses to airborne pathogens and intranasal vaccines. Here, we systematically investigated the mucosal humoral and cellular immune responses of NALTs in mice infected with A/Beijing/501/2009 (BJ501) and A/Puerto Rico/8/1934 (PR8) viruses. Compared with PR8 infection, BJ501 induced a more rapid increase of virus-specific IgA and IgG antibodies in the nasal lavage fluid and a higher ratio of IgG1/IgG2a, indicating a stronger Th2 response to BJ501 in mucosal immunity. In addition, using virus-specific enzyme-linked immunospot assay (ELISpot assay), we observed higher and earlier responses of virus-specific IgA and IgG antibody-secreting cells (ASCs) and IFN-γ and IL-4 cytokine-secreting cells (CSCs) in NALTs of mice intranasally infected with BJ501 virus. In particular, the frequency of BJ501-specific IFN-γ-CSCs significantly correlated with the kinetics of BJ501 virus load in NALTs, suggesting an important role of IFN-γ-CSCs-associated mucosal cellular immune responses in BJ501 virus clearance. Collectively, BJ501 induced a more comprehensive and rapid mucosal immune responses in NALTs of mice, providing further understanding of the immune responses elicited by 2009 pandemic H1N1 virus in upper respiratory tract. Keywords: nasal-associated lymphoid tissues (NALTs); influenza virus; mucosal immune response; Th1/Th2 response.


Assuntos
Imunidade Celular , Imunidade nas Mucosas , Vírus da Influenza A Subtipo H1N1 , Infecções por Orthomyxoviridae , Animais , Anticorpos Antivirais/sangue , Imunidade Celular/imunologia , Imunidade nas Mucosas/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Camundongos , Infecções por Orthomyxoviridae/imunologia
9.
Vet Microbiol ; 234: 77-82, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31213275

RESUMO

Control of currently circulating re-assorted low-pathogenicity avian influenza (LPAI) H9N2 is a major concern for both animal and human health. Thus, an improved LPAI H9N2 vaccination strategy is needed to induce complete immunity in chickens against LPAI H9N2 virus strains. Cytokines play a crucial role in mounting both the type and extent of an immune response generated following infection with a pathogen or after vaccination. To improve the efficacy of inactivated LPAI H9N2 vaccine, prokaryotic expression recombination chicken interferon-α (rchIFN-α) was used as vaccine adjuvant.In this study chIFN-α was used as adjuvant in inactivated AI H9N2 vaccine, modulated the immune response of chickens against the vaccine antigen through enhanced humoral and Th1-biased cell-mediated immunity, compared to chickens that received single AI H9N2 vaccine. To further test the protective efficacy of this improved vaccination regimen, immunized chickens were challenged with a high dose of LPAI H9N2 virus. Combined administration rchIFN-α showed markedly enhanced protection compared to single administration of the vaccine, as determined by mortality, clinical severity, and feed and water intake. This enhancement of protective immunity was further confirmed by reduced rectal shedding and replication of AIV H9N2 in challenged chickens. Our results indicate the value of combined administration of rchIFN-α to generate an effective immunization strategy in chickens against LPAI H9N2.


Assuntos
Imunogenicidade da Vacina , Vacinas contra Influenza/imunologia , Influenza Aviária/prevenção & controle , Interferon-alfa/genética , Adjuvantes Imunológicos , Animais , Anticorpos Antivirais/sangue , Galinhas , Imunidade Celular , Imunidade Humoral , Vírus da Influenza A Subtipo H9N2/imunologia , Vacinas contra Influenza/genética , Influenza Aviária/imunologia , Interferon-alfa/imunologia , Organismos Livres de Patógenos Específicos , Vacinas de Produtos Inativados/genética , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Eliminação de Partículas Virais
10.
World J Microbiol Biotechnol ; 35(6): 91, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31161259

RESUMO

The limited efficacy of available influenza vaccines against rapidly emerging new viral strains stresses the need for the development of new antigen-independent prophylactic treatment for enhancing immunity against influenza infection. Recent studies suggest that probiotics possess immunomodulatory properties and can reduce the severity of respiratory infections. Here, we investigated the potential of prophylactic Bifidobacterium bifidum in improving anti-influenza immune responses in an experimental lethal mouse-adapted influenza A (H1N1) infection in a BALB/c mouse model. One week after viral challenge, splenocyte proliferation assay (MTT), IFN-gamma, IL-12, and IL-4 in spleen and IL-6 in the lung homogenates were conducted using ELISA assays. Sera samples were collected to measure IgG1 and IgG2a levels. Furthermore, the mice challenged with lethal influenza virus were assessed for survival rate. The findings demonstrated a strong induction of both humoral and cellular immunities, as well as decreased level of IL-6 production in the lung and an increase in survival rate in the mice receiving Bifidobacterium than those of the control group were observed. Taken together, the results indicate a robust potential for Bifidobacterium to modulate humoral and cellular immune responses and induce balanced Th1/Th2 immune responses against influenza infection.


Assuntos
Bifidobacterium bifidum/fisiologia , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/tratamento farmacológico , Influenza Humana/imunologia , Probióticos/farmacologia , Animais , Proliferação de Células , Citocinas/metabolismo , Modelos Animais de Doenças , Cães , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Imunização , Imunoglobulina G/sangue , Imunomodulação , Vírus da Influenza A Subtipo H1N1/patogenicidade , Interferon gama/metabolismo , Interleucina-12/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Pulmão/imunologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Baço/imunologia , Taxa de Sobrevida , Células Th1/imunologia , Células Th2/imunologia
11.
World J Microbiol Biotechnol ; 35(6): 94, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31187291

RESUMO

Pseudomonas aeruginosa is the major infectious agent of concern for cystic fibrosis (CF) patients. Therefore, it is necessary to develop appropriate strategies for preventing colonization by this bacterium and/or neutralizing virulence factors. In this study, we formulated the encapsulation of exotoxin A into PLGA nanoparticles. The biological activities of the nanovaccine candidate were also characterized. Based on the results, ETA-PLGA can act as a suitable immunogen to stimulate the humoral and cellular immune response. The antibodies raised against ETA-PLGA significantly decreased bacterial titer in the spleens of the immunized mice after challenge with PAO1 strain, compared to the control groups. The encapsulation of PLGA into ETA led to a significantly higher production of INF-γ, TNF-α, IL-4, and IL-17A cytokine responses compared to the ETA group. ETA-PLGA enhanced IgG responses in immunized mice compared to ETA antigen. We concluded that encapsulation of Pseudomonas aeruginosa ETA to PLGA nanoparticles can increase its functional activity by decreasing the bacterial dissemination.


Assuntos
ADP Ribose Transferases/imunologia , Toxinas Bacterianas/imunologia , Exotoxinas/imunologia , Imunização , Nanoconjugados , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/imunologia , Infecções por Pseudomonas/prevenção & controle , Pseudomonas aeruginosa/patogenicidade , Vacinas Conjugadas , Fatores de Virulência/imunologia , ADP Ribose Transferases/uso terapêutico , Animais , Toxinas Bacterianas/uso terapêutico , Citocinas/metabolismo , Modelos Animais de Doenças , Exotoxinas/uso terapêutico , Feminino , Imunidade Celular , Imunidade Humoral , Imunoglobulina G/sangue , Interferon gama/metabolismo , Interleucina-17/metabolismo , Interleucina-4/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/uso terapêutico , Infecções por Pseudomonas/imunologia , Baço/imunologia , Baço/microbiologia , Fatores de Virulência/uso terapêutico
12.
Curr Protein Pept Sci ; 20(8): 770-776, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31060484

RESUMO

Acute kidney injury (AKI) is a systemic disease characterized by acute loss of renal function and accumulation of end products of nitrogen metabolism. Ischemic AKI is the most common cause of AKI, and inflammatory responses are inevitablely involved in ischemic AKI. In the process of ischemic AKI, multiple factors are involved in activating and recruitment of immune cell to the injured kidney. These factors include DAMPs and HIFs released from the injured kidney, increased expression of adhesion molecules, the production of chemokines and cytokines, activation of complement system and TLRs as well as the permeability dysfunction of the renal vascular endothelium. Immune cells of both the innate and adaptive immune systems, such as neutrophils, dendritic cells, macrophages and lymphocytes contribute to the pathogenesis of renal injury after ischemia reperfusion injury (IRI), with some of their subpopulations also participating in the repair process. Numerous studies of immune cells involved in the pathogenesis of AKI have enhanced the understanding of their possible mechanisms in AKI which might become the potential targets for the treatment of ischemic AKI. This review describes the function of the immune cells in the pathogenesis and repair of ischemic AKI and emphasizes the treatment of ischemic AKI potentially targeting them.


Assuntos
Lesão Renal Aguda/imunologia , Lesão Renal Aguda/patologia , Isquemia/metabolismo , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologia , Imunidade Adaptativa , Animais , Humanos , Imunidade Celular
13.
BMC Vet Res ; 15(1): 165, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118053

RESUMO

BACKGROUND: Feline infectious peritonitis (FIP) is considered highly fatal in its naturally occurring form, although up to 36% of cats resist disease after experimental infection, suggesting that cats in nature may also resist development of FIP in the face of infection with FIP virus (FIPV). Previous experimental FIPV infection studies suggested a role for cell-mediated immunity in resistance to development of FIP. This experimental FIPV infection study in specific pathogen free (SPF) kittens describes longitudinal antiviral T cell responses and clinical outcomes ranging from rapid progression, slow progression, and resistance to disease. RESULTS: Differences in disease outcome provided an opportunity to investigate the role of T cell immunity to FIP determined by T cell subset proliferation after stimulation with different viral antigens. Reduced total white blood cell (WBC), lymphocyte and T cell counts in blood were observed during primary acute infection for all experimental groups including cats that survived without clinical FIP. Antiviral T cell responses during early primary infection were also similar between cats that developed FIP and cats remaining healthy. Recovery of antiviral T cell responses during the later phase of acute infection was observed in a subset of cats that survived longer or resisted disease compared to cats showing rapid disease progression. More robust T cell responses at terminal time points were observed in lymph nodes compared to blood in cats that developed FIP. Cats that survived primary infection were challenged a second time to pathogenic FIPV and tested for antiviral T cell responses over a four week period. Nine of ten rechallenged cats did not develop FIP or T cell depletion and all cats demonstrated antiviral T cell responses at multiple time points after rechallenge. CONCLUSIONS: In summary, definitive adaptive T cell responses predictive of disease outcome were not detected during the early phase of primary FIPV infection. However emergence of antiviral T cell responses after a second exposure to FIPV, implicated cellular immunity in the control of FIPV infection and disease progression. Virus host interactions during very early stages of FIPV infection warrant further investigation to elucidate host resistance to FIP.


Assuntos
Coronavirus Felino/imunologia , Peritonite Infecciosa Felina/imunologia , Imunidade Celular , Linfócitos T/imunologia , Animais , Antígenos Virais/imunologia , Gatos , Resistência à Doença/imunologia , Organismos Livres de Patógenos Específicos
14.
Parasit Vectors ; 12(1): 233, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092283

RESUMO

BACKGROUND: Cryptosporidium parvum is a major cause of diarrhea in children and ruminants at the earliest stages of life. Maternal antibodies represent the main shield of neonate mammals for most of the infections. Two recombinant antigens (SA35 and SA40), portions of two C. parvum proteins, were tested for their ability to induce immune responses in adult mice and for protection on neonate BALB/c mice born from females immunised by mucosal delivery of both peptides. METHODS: Adult BALB/c mice were intraperitoneally immunised with SA35 and SA40, separately or mixed, and their immune response was characterised. Furthermore, BALB/c pregnant mice were immunised by mucosal delivery with an SA35/40 mix, before and during pregnancy. Soon after birth, their offspring were infected with two doses (1 × 105 and 5 × 103) of C. parvum oocysts and the parasitic burden was determined at 5 and 9 days post-infection. RESULTS: Intraperitoneal immunisation with SA35 and SA40 induced specific IgG and IgG1 in serum, specific IgA in the intestinal mucosa, increase of CD3+/CD4+ and CD30+ cells in splenocytes, which produced IFN-γ. Neonates born from immunised mice and infected with 1 × 105 oocysts showed a significant reduction of oocysts and intestinal forms (23 and 42%, respectively). A reduction of all parasitic forms (96%; P < 0.05) was observed when neonates were infected with 5 × 103 oocysts. CONCLUSIONS: SA35 and SA40 peptides induce specific humoral and cell-mediated immune responses to C. parvum in adult mice. Moreover, mucosal administration of the SA35/40 mix in pregnant mice reduces C. parvum burden in their litters.


Assuntos
Criptosporidiose/prevenção & controle , Imunidade Celular , Imunidade Humoral , Peptídeos/imunologia , Proteínas de Protozoários/imunologia , Vacinas Protozoárias/imunologia , Animais , Animais Recém-Nascidos , Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Criptosporidiose/imunologia , Cryptosporidium parvum , Feminino , Imunidade Materno-Adquirida , Imunização , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Mucosa Intestinal/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Oócitos/imunologia , Peptídeos/genética , Gravidez , Proteínas de Protozoários/genética
15.
MBio ; 10(3)2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088918

RESUMO

Candida yeasts are common commensals that can cause mucosal disease and life-threatening systemic infections. While many of the components required for defense against Candida albicans infection are well established, questions remain about how various host cells at mucosal sites assess threats and coordinate defenses to prevent normally commensal organisms from becoming pathogenic. Using two Candida species, C. albicans and C. parapsilosis, which differ in their abilities to damage epithelial tissues, we used traditional methods (pathogen CFU, host survival, and host cytokine expression) combined with high-resolution intravital imaging of transparent zebrafish larvae to illuminate host-pathogen interactions at the cellular level in the complex environment of a mucosal infection. In zebrafish, C. albicans grows as both yeast and epithelium-damaging filaments, activates the NF-κB pathway, evokes proinflammatory cytokines, and causes the recruitment of phagocytic immune cells. On the other hand, C. parapsilosis remains in yeast morphology and elicits the recruitment of phagocytes without inducing inflammation. High-resolution mapping of phagocyte-Candida interactions at the infection site revealed that neutrophils and macrophages attack both Candida species, regardless of the cytokine environment. Time-lapse monitoring of single-cell gene expression in transgenic reporter zebrafish revealed a partitioning of the immune response during C. albicans infection: the transcription factor NF-κB is activated largely in cells of the swimbladder epithelium, while the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) is expressed in motile cells, mainly macrophages. Our results point to different host strategies for combatting pathogenic Candida species and separate signaling roles for host cell types.IMPORTANCE In modern medicine, physicians are frequently forced to balance immune suppression against immune stimulation to treat patients such as those undergoing transplants and chemotherapy. More-targeted therapies designed to preserve immunity and prevent opportunistic fungal infection in these patients could be informed by an understanding of how fungi interact with professional and nonprofessional immune cells in mucosal candidiasis. In this study, we intravitally imaged these host-pathogen dynamics during Candida infection in a transparent vertebrate model host, the zebrafish. Single-cell imaging revealed an unexpected partitioning of the inflammatory response between phagocytes and epithelial cells. Surprisingly, we found that in vivo cytokine profiles more closely match in vitro responses of epithelial cells rather than phagocytes. Furthermore, we identified a disconnect between canonical inflammatory cytokine production and phagocyte recruitment to the site of infection, implicating noncytokine chemoattractants. Our study contributes to a new appreciation for the specialization and cross talk among cell types during mucosal infection.


Assuntos
Candidíase/imunologia , Citocinas/imunologia , Células Epiteliais/imunologia , Imunidade Celular , Microscopia Intravital , Macrófagos/microbiologia , Animais , Candida albicans , Candida parapsilosis , Candidíase/microbiologia , Células Epiteliais/microbiologia , Imunidade nas Mucosas , Larva/microbiologia , Fagócitos/imunologia , Fagócitos/microbiologia , Análise de Célula Única , Peixe-Zebra/microbiologia
16.
Cell Mol Life Sci ; 76(14): 2779-2788, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31101935

RESUMO

Avian virus infection remains one of the most important threats to the poultry industry. Pathogens such as avian influenza virus (AIV), avian infectious bronchitis virus (IBV), and infectious bursal disease virus (IBDV) are normally controlled by antibodies specific for surface proteins and cellular immune responses. However, standard vaccines aimed at inducing neutralizing antibodies must be administered annually and can be rendered ineffective because immune-selective pressure results in the continuous mutation of viral surface proteins of different strains circulating from year to year. Chicken T cells have been shown to play a crucial role in fighting virus infection, offering lasting and cross-strain protection, and offer the potential for developing universal vaccines. This review provides an overview of our current knowledge of chicken T cell immunity to viruses. More importantly, we point out the limitations and barriers of current research and a potential direction for future studies.


Assuntos
Infecções por Birnaviridae/imunologia , Imunidade Celular/imunologia , Vírus da Doença Infecciosa da Bursa/imunologia , Vírus da Influenza A/imunologia , Infecções por Orthomyxoviridae/imunologia , Linfócitos T/imunologia , Animais , Infecções por Birnaviridae/virologia , Galinhas , Infecções por Orthomyxoviridae/virologia
17.
J Anim Sci ; 97(7): 2739-2749, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31069378

RESUMO

The goal of this study was to compare the cell-mediated immune responses of highly commingled, sale-barn origin calves (STR; n = 10) to those of single source calves that had been weaned for 60 d (UNS; n = 10). Peripheral blood mononuclear cells and neutrophils (PMNs) were isolated from jugular venous blood of each calf. Peripheral blood mononuclear cells were stimulated with Concanavalin A (ConA), BVDV-1, BVDV-2, BHV-1, Mannheimia haemolytica, and Pasteurella multocida and evaluated for clonal proliferation and secretion of IL-8 into cell culture supernatants. The native functional capacities of PMNs were evaluated in response to stimulation with heat-killed Escherichia coli and Staphylococcus aureus. Complete blood counts and serum biochemical profiles were performed for each animal at the time of sample collection. Compared with STR calves, UNS calves had greater lymphocyte proliferative responses following stimulation BVDV1 (P = 0.041), BVDV2 (P = 0.002), BHV-1 (P = 0.001), M. haemolytica (P = 0.016), and P. multocida (P = 0.049). In addition, PMNs isolated from UNS calves had a greater ability to phagocytose E. coli (P = 0.001) and S. aureus (P = 0.003) when compared with STR calves. Serum nonesterified fatty acids were higher in STR calves (P < 0.001). Serum ß-hydroxybutyrate was lower in STR calves (P < 0.003). These data suggest that immunologic and physiologic differences exist between STR and UNS calves. Although the underlying mechanisms for these differences are not clear, it is possible that combinations of energy imbalances, stress-induced immunosuppression, and general immune naiveté may predispose STR calves to an increased risk of morbidity and mortality due to bovine respiratory disease.


Assuntos
Vacinas Bacterianas/imunologia , Doenças dos Bovinos/imunologia , Imunidade Celular , Vacinas Virais/imunologia , Animais , Bovinos , Doenças dos Bovinos/prevenção & controle , Concanavalina A/imunologia , Vírus da Diarreia Viral Bovina/imunologia , Escherichia coli/imunologia , Herpesvirus Bovino 1/imunologia , Leucócitos Mononucleares/imunologia , Masculino , Mannheimia haemolytica/imunologia , Neutrófilos/imunologia , Pasteurella multocida/imunologia , Distribuição Aleatória , Staphylococcus aureus/imunologia , Estresse Fisiológico , Vacinas Atenuadas/imunologia , Desmame
18.
Zhonghua Zhong Liu Za Zhi ; 41(5): 321-325, 2019 May 23.
Artigo em Chinês | MEDLINE | ID: mdl-31137163

RESUMO

Gastric cancer is the most common gastrointestinal cancer in China. The morbidity and mortality are extremely high and there are significant challenges in the treatment of gastric cancer. Recent studies have shown that the expressions of T lymphocyte subsets vary in the immune microenvironment of gastric cancer patients. T lymphocytes are not only the main effector cells of human cellular immunity, but also the important immunoregulatory cells. T lymphocytes not only reflect the state of the tumor microenvironment, but also closely relate with the prognosis of patients. T lymphocytes play a crucial guiding role in the clinical treatment. Currently, clinical trials related to immunological checkpoint inhibitors are still underway, among which PD-1/PD-L1 monoclonal antibody has been approved for the treatment of gastric cancer. The applications of tumor vaccines and adoptive cell therapies in gastric cancer are also being explored. How to screen patients suitable to immunotherapy, develop the best combination therapy and evaluate the effectiveness of immunotherapy need to be studied and solved.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunidade Celular/imunologia , Neoplasias Gástricas/imunologia , Subpopulações de Linfócitos T/imunologia , Microambiente Tumoral/imunologia , Antígeno B7-H1/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Pontos de Checagem do Ciclo Celular/imunologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/imunologia , Proteínas de Ciclo Celular/uso terapêutico , Humanos , Imunidade Celular/efeitos dos fármacos , Imunoterapia , Receptor de Morte Celular Programada 1/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos
19.
Parasit Vectors ; 12(1): 249, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113489

RESUMO

BACKGROUND: Whirling disease (WD), caused by the myxozoan parasite Myxobolus cerebralis, is responsible for high mortalities in rainbow trout hatcheries and natural populations. To elucidate how resistant and susceptible rainbow trout strains respond to early invasion, a well-established model of WD was used to demonstrate the kinetics of local and systemic immune responses in two rainbow trout strains, the susceptible American Trout Lodge (TL) and the more resistant German Hofer strain (HO). METHODS: Parasite load and cellular immune responses were compared across several time points after M. cerebralis exposure to elucidate the kinetics of immune cells in resistant and susceptible rainbow trout in response to early invasion. In the course of the 20 days following exposure, leukocyte kinetics was monitored by flow cytometry in the caudal fin (CF), head kidney (HK) and spleen (SP). For the analysis of the leukocyte composition, cells were stained using a set of monoclonal antibodies with known specificity for distinct subpopulations of rainbow trout leukocytes. RESULTS: Experiments indicated general increases of CF, HK and SP myeloid cells, while decreases of B cells and T cells in the SP and HK were observed at several time points in the TL strain. On the other hand, in the HO strain, increases of T cells were dominant in CF, HK and SP at multiple time points. The differences between HO and TL were most distinct at 2, 4, 12 and 48 hours post-exposure (hpe) as well as at 4 days post-exposure (dpe), with the vast majority of innate immune response cells having higher values in the susceptible TL strain. Alteration of the leukocyte populations with augmented local cellular responses and excessive immune reactions likely lead to subsequent host tissue damage and supports parasite invasion and development in TL. CONCLUSIONS: The findings of this study highlight the significance of effective local and systemic immune reaction and indicate proper activation of T lymphocytes critical for host resistance during M. cerebralis infection. The present study provides insights into the cellular basis of protective immune responses against M. cerebralis and can help us to elucidate the mechanisms underlying the variation in resistance to WD.


Assuntos
Suscetibilidade a Doenças , Doenças dos Peixes/imunologia , Linfócitos/imunologia , Oncorhynchus mykiss/parasitologia , Doenças Parasitárias em Animais/imunologia , Animais , Linfócitos B/imunologia , Modelos Animais de Doenças , Imunidade Celular , Imunidade Inata , Cinética , Myxobolus/imunologia , Carga Parasitária , Infecções por Protozoários/imunologia , Linfócitos T/imunologia
20.
Int J Nanomedicine ; 14: 3221-3234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123399

RESUMO

Background: Poly (lactic-co-glycolic acid) (PLGA) nanoparticles and surface modified PLGA nanoparticles have been widely studied as antigens or drugs carriers due to their controlled release characteristics and biocompatibility. However, most PLGA nanoparticles have lower antigens loading efficiency and adjuvanticity. Purpose: The aim of this study was to improve the antigen loading efficiency and adjuvant activity of PLGA nanoparticles. Materials and methods: Surface cationic polymer modification can improve the antigens loading efficiency of PLGA nanoparticles by surface adsorption. Therefore, in this study, chitosan modified PLGA nanoparticles (CS-AHPP/OVA), polyethyleneimine modified PLGA nanoparticles (PEI-AHPP/OVA), and ε-Poly-L-lysine modified PLGA nanoparticles (εPL-AHPP/OVA) were prepared as antigen delivery carriers to investigate the characterization and stability of these nanoparticles. These nanoparticles were evaluated for their efficacies as adjuvants pre- and post-modification. Results: The AHP and OVA-loaded PLGA nanoparticles (AHPP/OVA) were positively charged after surface cationic polymers modification, and their structural integrity was maintained. Their antigen loading capacity and stability of nanoparticles were improved by the surface cationic polymers modification. Increased positive surface charge resulted in greater OVA adsorption capacity. Among AHPP/OVA and the three surface cationic polymers synthesized from modified PLGA nanoparticles, PEI-AHPP/OVA showed the highest antigen loading efficiency and good stability. AHPP/OVA, CS-AHPP/OVA PEI-AHPP/OVA, and εPL-AHPP/OVA formulations significantly enhanced lymphocyte proliferation and improved the ratio of CD4+/CD8+ T cells. In addition, AHPP/OVA, PEI-AHPP/OVA and εPL-AHPP/OVA formulations induced secretion of cytokines (TNF-α, IFN-γ, IL-4, and IL-6), antibodies (IgG) and antibody subtypes (IgG1 and IgG2a) in immunized mice. These results demonstrate that these formulations generated a strong Th1-biased immune response. Among them, PEI-AHPP/OVA induced the strongest Th1-biased immune response. Conclusion: In conclusion, PEI-AHPP/OVA nanoparticles may be a potential antigen delivery system for the induction of strong immune responses.


Assuntos
Sistemas de Liberação de Medicamentos , Mel , Imunidade Celular , Ovalbumina/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polissacarídeos/química , Vacinas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Animais , Formação de Anticorpos , Antígenos/metabolismo , Cátions , Proliferação de Células , Quitosana/química , Citocinas/sangue , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Ativação Linfocitária , Camundongos Endogâmicos ICR , Nanopartículas/química , Ovalbumina/imunologia , Polietilenoimina/química , Baço/citologia , Linfócitos T/imunologia , Vacinação , Vacinas/imunologia
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