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1.
PLoS One ; 15(1): e0218905, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31935222

RESUMO

The innate immune response induced by type I interferons (IFNs) plays a critical role in the establishment of HIV infection. IFNs are induced early in HIV infection and trigger an antiviral defense program by signaling through the IFNα/ß receptor (IFNAR), which consists of two subunits, IFNAR1 and IFNAR2. Changes in IFNAR expression in HIV target cells, as well as other immune cells, could therefore have important consequences for initial HIV spread. It was previously reported that IFNAR2 expression is increased in peripheral blood CD4+ CXCR4+ T cells of HIV+ patients compared to HIV uninfected controls, suggesting that HIV infection may alter the IFN responsiveness of target cells. However, the earliest immune cells affected by HIV in vivo reside in the gut-associated lymphoid tissue (GALT). To date, it remains unknown if IFNAR expression is altered in GALT immune cells in the context of HIV infection and exposure to IFNs, including the 12 IFNα subtypes. Here, we analyzed the expression of surface bound and soluble IFNAR2 on Lamina propria mononuclear cells (LPMCs) isolated from the GALT of HIV- individuals and in plasma samples of HIV+ patients. IFNAR2 expression varied between different T cells, B cells and natural killer cells, but was not altered following HIV infection. Furthermore, expression of the soluble IFNAR2a isoform was not changed in HIV+ patients compared to healthy donors, nor in LPMCs after HIV-1 infection ex vivo. Even though the 12 human IFNα subtypes trigger different biological responses and vary in their affinity to both receptor subunits, stimulation of LPMCs with different recombinant IFNα subtypes did not result in any significant changes in IFNAR2 surface expression. Our data suggests that potential changes in the IFN responsiveness of mucosal immune cells during HIV infection are unlikely dictated by changes in IFNAR2 expression.


Assuntos
Infecções por HIV/genética , Imunidade Inata/genética , Receptor de Interferon alfa e beta/genética , Antivirais/farmacologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Imunidade nas Mucosas/imunologia , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , Tecido Linfoide/imunologia , Tecido Linfoide/virologia , Transdução de Sinais/efeitos dos fármacos
2.
Adv Exp Med Biol ; 1197: 11-26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31732931

RESUMO

The long-standing dogma that immunological memory is the exclusive prerogative of the adaptive immune system has been challenged by emerging evidence that innate immunity can also maintain memory of past events. Such immunological imprinting takes two forms, trained innate immunity and tolerance. Trained immunity involves metabolic and epigenetic adaptations in innate immune cells and their progenitors in the bone marrow upon exposure to certain microbial and/or inflammatory stimuli so that the "trained" cells would be poised to respond much faster and stronger to a subsequent challenge (e.g., a new infection that is not necessarily the same as the earlier one). Conversely, tolerance leads to attenuated immune responses to secondary stimuli. This review focuses on trained immunity and discusses evidence for its existence from lower organisms to humans, its mechanistic underpinnings, and its translational ramifications. Although trained immunity can be considered as an evolutionarily conserved beneficial response against reinfections, in the setting of modern societies with high prevalence of chronic mucosal and systemic inflammatory diseases, trained immunity could also promote maladaptive immune responses that aggravate pathology. Thus, depending on context, innate immune memory could be therapeutically manipulated using defined agonists to either promote innate immune responses (particularly useful for the treatment of infections or chemotherapy-induced myelosuppression) or suppress excessive inflammation in inflammatory and autoimmune diseases.


Assuntos
Imunidade Inata , Imunidade nas Mucosas , Memória Imunológica , Humanos , Imunidade Inata/imunologia , Imunidade nas Mucosas/imunologia , Inflamação
3.
Vet Clin North Am Food Anim Pract ; 35(3): 431-451, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31590896

RESUMO

This article discusses key concepts important for mucosal immunity. The mucosa is the largest immune organ of the body. The mucosal barrier (the tight junctions and the "kill zone") along with the mucosa epithelial cells maintaining an anti-inflammatory state are essential for the mucosal firewall. The microbiome (the microorganisms that are in the gastrointestinal, respiratory, and reproductive tract) is essential for immune development, homeostasis, immune response, and maximizing animal productivity. Mucosal vaccination provides an opportunity to protect animals from most infectious diseases because oral, gastrointestinal, respiratory, and reproductive mucosa are the main portals of entry for infectious disease.


Assuntos
Bovinos/imunologia , Imunidade nas Mucosas/imunologia , Animais , Feminino , Imunidade Celular , Imunidade Humoral
4.
Vet Clin North Am Food Anim Pract ; 35(3): 485-505, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31590899

RESUMO

New insights into the host-microbiota relationship have recently emerged with the advancement of molecular technologies such as next-generation sequencing. This article presents the current knowledge regarding the interaction between bacteria and the immune system of the gut, the uterus, and the mammary gland of cattle.


Assuntos
Bovinos/imunologia , Bovinos/microbiologia , Sistema Imunitário/microbiologia , Microbiota/imunologia , Animais , Feminino , Imunidade nas Mucosas/imunologia
5.
Mol Immunol ; 114: 497-512, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31518854

RESUMO

Compounding with the problem of frequent antigenic shift and occasional drift of the segmented genome of Avian Influenza Virus (AIV), vaccines based on major surface glycoproteins such as haemagglutinin (HA) to counter heterosubtypic AIV infection in chickens remain unsuccessful. In contrast, neuraminidase (NA), the second most abundant surface glycoprotein present in viral capsid is less mutable and, in some instances, successful in eliciting inter-species cross-reactive antibody responses. However, without selective activation of B-cells and T-cells, the ability of NA to induce strong cell mediated immune responses is limited, thus NA based vaccines cannot singularly address the risk of virus escape from host defence. To this end, the highly conserved ectodomain of influenza matrix protein-2 (M2e) has emerged as an attractive cross-protective vaccine target. The present study describes the potential of recombinant Lactococcus lactis (rL. lactis) in expressing functional influenza NA or M2e proteins and conferring effective mucosal and systemic immune responses in the intestine as well as in the upper respiratory airways (trachea) of chickens. In addition, lavages collected from trachea and intestine of birds administered with rL. lactis expressing influenza NA or M2e protein were found to protect MDCK cells against avian influenza type A/PR/8/34 (H1N1) virus challenge. Although minor, the differences in the expression of pro-inflammatory cytokines gene transcripts targeted in this study among the birds administered with either empty or rL. lactis could be attributed to the activation of innate response by L. lactis.


Assuntos
Galinhas/imunologia , Imunidade nas Mucosas/imunologia , Influenza Aviária/imunologia , Lactococcus lactis/imunologia , Neuraminidase/imunologia , Proteínas da Matriz Viral/imunologia , Animais , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Galinhas/virologia , Reações Cruzadas/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Linfócitos T/imunologia , Vacinação/métodos
6.
J Immunoassay Immunochem ; 40(6): 630-641, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31544580

RESUMO

The emergence of antigenic variants and very virulent strains of infectious bursa disease virus (IBDV) in vaccinated flocks considerably stimulated research in IBDV vaccine administration. The mucoadhesive and immunopotentials of Cedrela odorata and Khaya senegalensis were explored in vaccine delivery against clinical IBDV in broiler chickens. A total of 400 chicks were successfully brooded and raised from day old for commencement of this experiment. The birds were randomly distributed into eight groups with an average of 50 birds per group comprising: Gums-Gumboro Vaccine Ocular (infected) (GGVOC), Gumboro Vaccine alone Ocular (infected) (GVOC), Gums alone Ocular (infected) (GOC), Gums-Gumboro Vaccine Oral (infected) (GGVOR), Gumboro Vaccine alone Oral (infected) (GVOR), Gums alone Oral (infected) (GOR), No-Vaccine-No-Gums (infected) (NVNG/i), and No-Vaccine-No-Gums (not infected) (NVNG). On a weekly basis, 1.5mls of blood were collected from 5 birds and 3 birds euthanized per group for serological analysis and mucosal washings (trachea and intestine) respectively. Data obtained were analyzed and sample to positive ratio calculated. The post 1st vaccination trachea IgG antibody response was moderately higher in the ocular groups than the oral groups. It was also high in the VOC, GVOC, GOC, VOR groups than the GVOR groups. The antibody response (IgG) pre and post 1st vaccination, post 2nd vaccination and post infection from serum, trachea and intestinal washes showed that by week 1 Post 1st vaccination, there was insignificant increase in titer serum response of the gum-vaccine ocular group compared to the vaccine ocular alone while both groups were insignificantly higher than the oral group. Overall, serum titer showed a rapid response with spiked significant response by 48h pi in the gum vaccine groups (especially GVOR), which peaks by day 3 and remains insignificantly higher throughout the day 7 pi compared to vaccine alone groups. In conclusion, use of the mucilage from C. odorata and K. senegalenses in equal proportion has given better enhancement of the response to IBDV vaccination and premise for further investigations for improvement against IBD.


Assuntos
Infecções por Birnaviridae/imunologia , Cedrela/imunologia , Imunidade nas Mucosas/imunologia , Vírus da Doença Infecciosa da Bursa/imunologia , Meliaceae/imunologia , Doenças das Aves Domésticas/imunologia , Vacinas Virais/imunologia , Animais , Galinhas , Gomas Vegetais , Doenças das Aves Domésticas/virologia , Vacinação , Vacinas Virais/administração & dosagem
7.
Protein Pept Lett ; 26(12): 904-909, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31429685

RESUMO

BACKGROUND: Rotavirus is the most common cause of infectious diarrhea in infants and young children around the world. The inner capsid protein VP6 has been discussed as alternative vaccine as it can induce cross-protective immune responses against different RV strai. The use of ferritin nanoparticle may enhance the immunogenicity of the subunit vaccine. OBJECTIVE: In this article, our motivation is to design and obtain a self-assemble rotavirus nanoparticle vaccine which can induce efficiency immune response. METHODS: The VP6 protein was fused with ferritin and expressed in the Escherichia coli expression system. The recombinant VP6-ferritin (rVP6-ferritin) protein was purified by His-tag affinity chromatography and fast protein liquid chromatography. Transmission electron micrographic analysis was used to detect the nanostructure of the self-assembled protein. Mice were gavage with the protein and ELISA was used to detect the titer of the VP6 specific antibody. RESULTS: The recombined VP6-ferritin was expressed in the Escherichia coli as an inclusion body form and the purified protein has similar antigenicity to rotavirus VP6. Transmission electron micrographic analysis of rVP6-ferritin exhibited spherical architecture with a uniform size distribution, which is similar to the ferritin nanocage. Immune response analysis showed that mice immunized by rVP6-ferritin protein induced 8000 (8000±1093) anti-VP6 IgG titers or 1152 (1152±248.8) anti-VP6 IgA titers. CONCLUSION: According to the above research, the rotavirus VP6-ferritin protein can be easily express and self-assemble to the nano-vaccine and induce efficiency humoral and mucosal immunity. Our research makes a foundation for the development of oral rotavirus vaccine.


Assuntos
Antígenos Virais/imunologia , Proteínas do Capsídeo/imunologia , Escherichia coli/metabolismo , Imunidade nas Mucosas/imunologia , Nanopartículas , Proteínas Recombinantes de Fusão/imunologia , Vacinas contra Rotavirus/imunologia , Rotavirus/imunologia , Animais , Anticorpos Antivirais/imunologia , Antígenos Virais/genética , Proteínas do Capsídeo/genética , Escherichia coli/genética , Feminino , Ferritinas/genética , Humanos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes de Fusão/genética , Vacinas contra Rotavirus/genética
8.
Cells ; 8(7)2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31295951

RESUMO

Mucosal surfaces play a central role in the pathogenesis of rheumatoid arthritis (RA). Several risk factors, such as cigarette smoking, environmental pollution, and periodontitis interact with the host at the mucosal level, triggering immune system activation. Moreover, the alteration of microbiota homeostasis is gaining increased attention for its involvement in the disease pathogenesis, modulating the immune cell response at a local and subsequently at a systemic level. Currently, the onset of the clinical manifest arthritis is thought to be the last step of a series of pathogenic events lasting years. The positivity for anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF), in absence of symptoms, characterizes a preclinical phase of RA-namely systemic autoimmune phase- which is at high risk for disease progression. Several immune abnormalities, such as local ACPA production, increased T cell polarization towards a pro-inflammatory phenotype, and innate immune cell activation can be documented in at-risk subjects. Many of these abnormalities are direct consequences of the interaction between the environment and the host, which takes place at the mucosal level. The purpose of this review is to describe the humoral and cellular immune abnormalities detected in subjects at risk of RA, highlighting their origin from the mucosa-environment interaction.


Assuntos
Artrite Reumatoide/metabolismo , Imunidade nas Mucosas/imunologia , Membrana Mucosa/imunologia , Anticorpos Anti-Proteína Citrulinada/imunologia , Anticorpos Anti-Proteína Citrulinada/metabolismo , Artrite Reumatoide/fisiopatologia , Autoanticorpos/genética , Autoantígenos/imunologia , Progressão da Doença , Interação Gene-Ambiente , Humanos , Membrana Mucosa/fisiologia , Fator Reumatoide/genética
9.
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
10.
Biomed Res Int ; 2019: 2323540, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119156

RESUMO

Bifidobacterium animalis subsp. lactis IPLA 20020 and Lactobacillus gasseri IPLA 20212, two strains isolated from human samples, were evaluated for safety and influence over the intestinal microbiota and cytokine production by the intestinal tissue of adult BALB/c mice. Mice were divided into four groups receiving during 8 days PBS or a suspension of each strain, prepared fresh or lyophilized (bifidobacteria), at an amount of 4x108 viable cells/day. This dose could be comparable to the probiotic intake of a human adult who consumed about 100-200 mL of functional fermented milk per day, considering the usual level of probiotics in commercial products. No microbial translocation to liver or alterations in food intake, weight, and behavior were observed in treated mice. Intestinal content of secretory immunoglobulin A (s-IgA) was not affected, discarding any adverse effect on the mucosa-associated immunity. The profile of intestinal proinflammatory/regulatory cytokines after intervention evidenced that the microbial strain administered and its cellular state (fresh or lyophilized) as well as the host tissue analyzed (small or large intestine) influenced the immune response and suggests a moderate shift towards a T helper 1 profile (Th1) in the large intestine after the administration of both strains. Changes on relative levels of some intestinal microbial groups were evidenced after intervention. It is noteworthy that butyrate was positively associated with a balanced pro-Th1 immune response. Therefore, B. animalis subsp. lactis IPLA20020 and L. gasseri IPLA 20212 could be considered potential probiotic candidates to be included in functional foods for balancing the intestinal immune response.


Assuntos
Bifidobacterium/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade nas Mucosas/imunologia , Lactobacillus/imunologia , Animais , Bifidobacterium/crescimento & desenvolvimento , Fermentação , Humanos , Imunomodulação/genética , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Intestinos/imunologia , Intestinos/microbiologia , Lactobacillus/crescimento & desenvolvimento , Camundongos , Probióticos , Células Th1/imunologia , Células Th1/microbiologia
11.
Int J Oral Sci ; 11(2): 16, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31068577

RESUMO

Opportunistic bacteria in apical periodontitis (AP) may pose a risk for systemic dissemination. Mucosal-associated invariant T (MAIT) cells are innate-like T cells with a broad and potent antimicrobial activity important for gut mucosal integrity. It was recently shown that MAIT cells are present in the oral mucosal tissue, but the involvement of MAIT cells in AP is unknown. Here, comparison of surgically resected AP and gingival tissues demonstrated that AP tissues express significantly higher levels of Vα7.2-Jα33, Vα7.2-Jα20, Vα7.2-Jα12, Cα and tumour necrosis factor (TNF), interferon (IFN)-γ and interleukin (IL)-17A transcripts, resembling a MAIT cell signature. Moreover, in AP tissues the MR1-restricted MAIT cells positive for MR1-5-OP-RU tetramer staining appeared to be of similar levels as in peripheral blood but consisted mainly of CD4+ subset. Unlike gingival tissues, the AP microbiome was quantitatively impacted by factors like fistula and high patient age and had a prominent riboflavin-expressing bacterial feature. When merged in an integrated view, the examined immune and microbiome data in the sparse partial least squares discriminant analysis could identify bacterial relative abundances that negatively correlated with Vα7.2-Jα33, Cα, and IL-17A transcript expressions in AP, implying that MAIT cells could play a role in the local defence at the oral tissue barrier. In conclusion, we describe the presence of MAIT cells at the oral site where translocation of oral microbiota could take place. These findings have implications for understanding the immune sensing of polymicrobial-related oral diseases.


Assuntos
Imunidade nas Mucosas/imunologia , Microbiota , Células T Invariáveis Associadas à Mucosa , Periodontite Periapical/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Células T Matadoras Naturais/imunologia , Periodontite Periapical/microbiologia
12.
J Immunol Res ; 2019: 8303648, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949518

RESUMO

Vaccines are recognized worldwide as one of the most important tools for combating infectious diseases. Despite the tremendous value conferred by currently available vaccines toward public health, the implementation of additional vaccine platforms is also of key importance. In fact, currently available vaccines possess shortcomings, such as inefficient triggering of a cell-mediated immune response and the lack of protective mucosal immunity. In this regard, recent work has been focused on vaccine delivery systems, as an alternative to injectable vaccines, to increase antigen stability and improve overall immunogenicity. In particular, novel strategies based on edible or intradermal vaccine formulations have been demonstrated to trigger both a systemic and mucosal immune response. These novel vaccination delivery systems offer several advantages over the injectable preparations including self-administration, reduced cost, stability, and elimination of a cold chain. In this review, the latest findings and accomplishments regarding edible and intradermal vaccines are described in the context of the system used for immunogen expression, their molecular features and capacity to induce a protective systemic and mucosal response.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Absorção Cutânea , Vacinação/métodos , Vacinas de Plantas Comestíveis , Vacinas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Administração Oral , Animais , Ensaios Clínicos como Assunto , Doenças Transmissíveis/imunologia , Técnicas de Transferência de Genes , Humanos , Imunidade Celular , Imunidade nas Mucosas/imunologia , Imunogenicidade da Vacina , Camundongos , Vacinas/imunologia
13.
Clin Exp Immunol ; 196(2): 205-214, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30963541

RESUMO

There is an urgent and unmet need to develop effective vaccines to reduce the global burden of infectious disease in both animals and humans, and in particular for the majority of pathogens that infect via mucosal sites. Here we summarise the impediments to developing mucosal vaccines and review the new and emerging technologies aimed at overcoming the lack of effective vaccine delivery systems that is the major obstacle to developing new mucosal vaccines.


Assuntos
Imunidade nas Mucosas/imunologia , Membrana Mucosa/imunologia , Vacinas/imunologia , Animais , Sistemas de Liberação de Medicamentos/métodos , Humanos , Vacinação/métodos
14.
Fish Shellfish Immunol ; 89: 428-436, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30978446

RESUMO

Fish skin mucus is a viscous and semipermeable barrier made mainly of water, glycoproteins and soluble proteins. It represents an important defence against the environment and previous studies have reported the presence of different substances involved in immune defence responses in it. The aim of the present work was to characterize skin mucus protease activity by zymography and esterase activity of the subfamily of carboxylesterases in three species of interest for aquaculture: gilthead sea bream, sea bass and meagre. Mucus antioxidant power was also determined by adapting ferric reducing antioxidant power (FRAP) analysis. As a result of these non-specific immune defence parameters, we compared the antibacterial capacity of skin mucus in these species via in vitro dual bacteria strains-skin mucus co-culture growths. We used Pseudomonas anguilliseptica and Vibrio anguillarum as marine pathogenic bacteria and Escherichia coli as non-pathogenic. For each fish species, in the respective zymograms, we determined a pattern of proteolytic digestion bands. A high-molecular-weight band (around 200 kDa; H-band) was evident in sea bream and sea bass, and showed chymotrypsin activity. One or two intermediate-molecular-weight bands (around 75 kDa; I-bands) with non-trypsin and non-chymotrypsin activity, and putatively with metalloprotease activity, were evident in all species. Finally, low-molecular-weight bands (between 14 and 30 kDa; L-bands) showed distinct patterns for each species and matched trypsin activity. Despite the conservative pattern of digestion bands, the levels of total proteolytic activity (TPA) were 5 and 10 times higher in meagre than in sea bass and sea bream, respectively. In parallel, three carboxylesterase activities were detected in the mucus of the three fish species, using myristate (pNPM-CE activity), butyrate (pNPB-CE activity) and acetate (pNPA-CE activity) as substrates. Both pNPB-CE and pNPA-CE were the most abundant in fish mucus, and meagre was again the species with the highest levels. In contrast, the antioxidant power of meagre skin mucus was the lowest. We established the capacity of skin mucus to block or limit bacterial growth (lytic activity) using 24 h growth curves. The log-growth phase of V. anguillarum was strongly blocked by sea bream and meagre mucus for a few hours; but not by sea bass mucus. However, if mucus was not renewed, log-growth was at the end of 24 h studied period. For its part, P. anguilliseptica growth curve was delayed by the three mucus types during the entire growth period. Only meagre achieved lytic activity against E. coli growth. All parameters studied here will be of a great interest as non-invasive bioindicators of non-specific immune defences in fish skin mucus.


Assuntos
Carboxilesterase/metabolismo , Proteínas de Peixes/metabolismo , Imunidade nas Mucosas/imunologia , Muco/imunologia , Perciformes/imunologia , Animais , Bass/imunologia , Muco/enzimologia , Pele/enzimologia , Pele/imunologia
15.
Proc Natl Acad Sci U S A ; 116(13): 6286-6291, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30862736

RESUMO

Disruption of mucosal immunity plays a critical role in the pathogenesis of inflammatory bowel disease, yet its mechanism remains not fully elucidated. Here, we found that activating transcription factor 3 (ATF3) protects against colitis by regulating follicular helper T (TFH) cells in the gut. The expression of ATF3 in CD4+ T cells was negatively correlated with the severity of ulcerative colitis in clinical patients. Mice with ATF3 deficiency in CD4+ T cells (CD4 cre Atf3 fl/fl ) were much more susceptible to dextran sulfate sodium-induced colitis. The frequencies of TFH cells, not other T cell subsets, were dramatically decreased in Peyer's patches from CD4 cre Atf3 fl/fl mice compared with Atf3 fl/fl littermate controls. The defective TFH cells significantly diminished germinal center formation and IgA production in the gut. Importantly, adoptive transfer of TFH or IgA+ B cells caused significant remission of colitis in CD4 cre Atf3 fl/fl mice, indicating the TFH-IgA axis mediated the effect of ATF3 on gut homeostasis. Mechanistically, B cell lymphoma 6 was identified as a direct transcriptional target of ATF3 in CD4+ T cells. In summary, we demonstrated ATF3 as a regulator of TFH cells in the gut, which may represent a potential immunotherapeutic target in colitis.


Assuntos
Fator 3 Ativador da Transcrição/imunologia , Fator 3 Ativador da Transcrição/farmacologia , Colite/tratamento farmacológico , Colite/imunologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologia , Fator 3 Ativador da Transcrição/genética , Fator 3 Ativador da Transcrição/metabolismo , Transferência Adotiva , Animais , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Colite/patologia , Colite Ulcerativa , Colo/patologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Homeostase , Imunidade nas Mucosas/imunologia , Imunoglobulina A , Imunoterapia , Camundongos , Nódulos Linfáticos Agregados/imunologia , Subpopulações de Linfócitos T
16.
Carbohydr Polym ; 213: 100-111, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30879649

RESUMO

Nasal immunization to prevent and treat diseases caused by infection through the respiratory tract cannot be actualized because of the lack of effective adjuvants. We have proven that compared with antigens loaded on CS or O-HTCC alone in nasal vaccination, antigens loaded on the nanoparticles of curdlan sulfate/O-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (CS/O-HTCC) can induce stronger systemic and mucosal immune responses. In this study, we evaluated the immunostimulatory activity and mechanisms of CS/O-HTCC nanoparticles. The results showed that CS/O-HTCC nanoparticles can improve the activation of antigen-presenting cells, upregulate the production of inflammatory factors and cytokines, induce cross-presentation, and simultaneously activate type I interferon-related genes. CS/O-HTCC nanoparticles also activated the PI3K/AKT and MAPK pathways and significantly promoted IL-2 transcription to induce the proliferation of lymphocytes. The results revealed that CS/O-HTCC nanoparticles as a type of multifunctional adjuvant can improve multiple arms of immune responses.


Assuntos
Adjuvantes Imunológicos/farmacologia , Quitosana/farmacologia , Nanopartículas/química , beta-Glucanas/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/química , Animais , Quitosana/administração & dosagem , Quitosana/química , Feminino , Imunidade nas Mucosas/efeitos dos fármacos , Imunidade nas Mucosas/imunologia , Injeções Intraperitoneais , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , beta-Glucanas/administração & dosagem , beta-Glucanas/química
17.
Nat Immunol ; 20(5): 593-601, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30886417

RESUMO

Interferon-λ (IFN-λ) acts on mucosal epithelial cells and thereby confers direct antiviral protection. In contrast, the role of IFN-λ in adaptive immunity is far less clear. Here, we report that mice deficient in IFN-λ signaling exhibited impaired CD8+ T cell and antibody responses after infection with a live-attenuated influenza virus. Virus-induced release of IFN-λ triggered the synthesis of thymic stromal lymphopoietin (TSLP) by M cells in the upper airways that, in turn, stimulated migratory dendritic cells and boosted antigen-dependent germinal center reactions in draining lymph nodes. The IFN-λ-TSLP axis also boosted production of the immunoglobulins IgG1 and IgA after intranasal immunization with influenza virus subunit vaccines and improved survival of mice after challenge with virulent influenza viruses. IFN-λ did not influence the efficacy of vaccines applied by subcutaneous or intraperitoneal routes, indicating that IFN-λ plays a vital role in potentiating adaptive immune responses that initiate at mucosal surfaces.


Assuntos
Imunidade Adaptativa/imunologia , Citocinas/imunologia , Imunidade nas Mucosas/imunologia , Interleucinas/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Imunidade Adaptativa/genética , Animais , Formação de Anticorpos/efeitos dos fármacos , Formação de Anticorpos/imunologia , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/virologia , Imunidade nas Mucosas/efeitos dos fármacos , Imunidade nas Mucosas/genética , Imunização/métodos , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/imunologia , Vírus da Influenza A/fisiologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Interleucinas/administração & dosagem , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Knockout , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/virologia , Receptores de Interferon/genética , Receptores de Interferon/imunologia , Receptores de Interferon/metabolismo
18.
J Immunol ; 202(7): 2044-2056, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30760622

RESUMO

Deregulated immune response to a dysbiotic resident microflora within the oral cavity leads to chronic periodontal disease, local tissue destruction, and various systemic complications. To preserve tissue homeostasis, inflammatory signaling pathways involved in the progression of periodontitis must be tightly regulated. A20 (TNFAIP3), a ubiquitin-editing enzyme, has emerged as one of the key regulators of inflammation. Yet, the function of A20 in the oral mucosa and the biological pathways in which A20 mitigates periodontal inflammation remain elusive. Using a combination of in vivo and ex vivo disease models, we report in this study that A20 regulates inflammatory responses to a keystone oral bacterium, Porphyromonas gingivalis, and restrains periodontal inflammation through its effect on NF-κB signaling and cytokine production. Depletion of A20 using gene editing in human macrophage-like cells (THP-1) significantly increased cytokine secretion, whereas A20 overexpression using lentivirus infection dampened the cytokine production following bacterial challenge through modulating NF-κB activity. Similar to human cells, bone marrow-derived macrophages from A20-deficient mice infected with P. gingivalis displayed increased NF-κB activity and cytokine production compared with the cells isolated from A20-competent mice. Subsequent experiments using a murine ligature-induced periodontitis model showed that even a partial loss of A20 promotes an increased inflammatory phenotype and more severe bone loss, further verifying the critical function of A20 in the oral mucosa. Collectively, to our knowledge, these findings reveal the first systematic evidence of a physiological role for A20 in the maintenance of oral tissue homeostasis as a negative regulator of inflammation.


Assuntos
Inflamação/imunologia , Mucosa Bucal/imunologia , NF-kappa B/imunologia , Periodontite/imunologia , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/imunologia , Animais , Células HEK293 , Humanos , Imunidade nas Mucosas/imunologia , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mucosa Bucal/metabolismo , NF-kappa B/metabolismo , Periodontite/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo
19.
Biosci Rep ; 39(3)2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30808716

RESUMO

Porcine epidemic diarrhea (PED) is a highly contagious disease in newborn piglets and causes substantial economic losses in the world. PED virus (PEDV) spreads by fecal-oral contact and can be prevented by oral immunization. Therefore, it is necessary to develop an effective oral vaccine against PEDV infection. Currently, Bacillus subtilis as recombinant vaccine carrier has been used for antigen delivery and proved well in immune effect and safety. The present study evaluated the immunogenicity of recombinant Bacillus subtilis (B. subtilis-RC) in piglets via oral administration. After oral immunization in piglets, B. subtilis-RC significantly increased the local mucosal immune responses. Oral administration with B. subtilis-RC significantly improved the level of specific mucosal immunoglobulin A (IgA) antibodies against PEDV infection, through enlarging the area of Peyer's patches (PPs) and increasing the number of ileum IgA+ secreting (SIgA) cells. In the meantime, B. subtilis-RC remarkably increased the number of intraepithelial lymphocytes (IELs). We also observed that oral administration of B. subtilis-RC significantly increased CD3+T lymphocytes' numbers and up-regulated the ratio of CD4+/CD8+ T cells. Furthermore, high titers of specific serum immunoglobulin G (IgG) revealed satisfactory systemic immune response against PEDV infection. In summary, our study demonstrated that oral administration of B. subtilis-RC could trigger a high level of local and systemic immune responses and would be a promising candidate vaccine against PEDV infection in piglets.


Assuntos
Antígenos Virais/imunologia , Bacillus subtilis/imunologia , Infecções por Coronavirus/imunologia , Imunidade nas Mucosas/imunologia , Vírus da Diarreia Epidêmica Suína/imunologia , Doenças dos Suínos/imunologia , Administração Oral , Animais , Animais Recém-Nascidos , Anticorpos Antivirais/imunologia , Antígenos Virais/genética , Bacillus subtilis/genética , Relação CD4-CD8 , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Humanos , Imunoglobulina A/imunologia , Vírus da Diarreia Epidêmica Suína/fisiologia , Suínos , Doenças dos Suínos/virologia , Linfócitos T
20.
J Infect Dis ; 219(12): 1963-1968, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-30721997

RESUMO

Lactoferrin modulates mucosal immunity and targets mechanisms contributing to inflammation during human immunodeficiency virus disease. A randomized placebo-controlled crossover clinical trial of recombinant human (rh) lactoferrin was conducted among 54 human immunodeficiency virus-infected participants with viral suppression. Outcomes were tolerability, inflammatory, and immunologic measures, and the intestinal microbiome. The median age was 51 years, and the median CD4+ cell count was 651/µL. Adherence and adverse events did not differ between rh-lactoferrin and placebo. There was no significant effect on plasma interleukin-6 or D-dimer levels, nor on monocyte/T-cell activation, mucosal integrity, or intestinal microbiota diversity. Oral administration of rh-lactoferrin was safe but did not reduce inflammation and immune activation. Clinical Trials Registration: NCT01830595.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Imunidade nas Mucosas/efeitos dos fármacos , Lactoferrina/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Proteínas Recombinantes de Fusão/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Feminino , HIV/efeitos dos fármacos , HIV/imunologia , Infecções por HIV/virologia , Humanos , Imunidade nas Mucosas/imunologia , Inflamação/tratamento farmacológico , Inflamação/virologia , Interleucina-6/metabolismo , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Carga Viral/efeitos dos fármacos
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