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1.
Dev Comp Immunol ; 138: 104523, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36055417

RESUMO

Silica crystals are potent activators of the inflammasome that cause a fibrotic lung disease, called silicosis, with no effective treatment available. We report here that injection of silica crystals into the hindbrain ventricle of zebrafish embryos led to the initiation of local and systemic immune responses driven through both Toll-like receptors (TLR)- and inflammasome-dependent signaling pathways, followed by induction of pro-fibrotic markers. Genetic and pharmacological analysis revealed that the Nlrp3 inflammasome regulated silica crystal-induced inflammation and pyroptotic cell death, but not emergency myelopoiesis. In addition, Cxcl8a/Cxcr2-dependent recruitment of myeloid cells to silica crystals was required to promote emergency myelopoiesis and systemic inflammation. The zebrafish model of silicosis developed here shed light onto the molecular mechanisms involved in the activation of the immune system by silica crystals.


Assuntos
Inflamassomos , Silicose , Animais , Imunidade , Inflamassomos/metabolismo , Inflamação , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Dióxido de Silício/efeitos adversos , Receptores Toll-Like/metabolismo , Peixe-Zebra/metabolismo
2.
Methods Mol Biol ; 2552: 283-294, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36346598

RESUMO

Antibody and TCR modeling are becoming important as more and more sequence data becomes available to the public. One of the pressing questions now is how to use such data to understand adaptive immune responses to disease. Infectious disease is of particular interest because the antigens driving such responses are often known to some extent. Here, we describe tips for gathering data and cleaning it for use in downstream analysis. We present a method for high-throughput structural modeling of antibodies or TCRs using Repertoire Builder and its extensions. AbAdapt is an extension of Repertoire Builder for antibody-antigen docking from antibody and antigen sequences. ImmuneScape is a corresponding extension for TCR-pMHC 3D modeling. Together, these pipelines can help researchers to understand immune responses to infection from a structural point of view.


Assuntos
Antígenos , Receptores de Antígenos de Linfócitos T , Imunidade
3.
Gen Comp Endocrinol ; 330: 114139, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36209834

RESUMO

Defenses against pathogens can take on many forms. For instance, behavioral avoidance of diseased conspecifics is widely documented. Interactions with these infectious conspecifics can also, however, lead to physiological changes in uninfected animals, an effect that is much less well understood. These changes in behavior and physiology are particularly important to study in a reproductive context, where they can impact reproductive decisions and offspring quality. Here, we studied how an acute (3 h) exposure to an immune-challenged male affected female blood transcriptomics and behavior. We predicted that females paired with immune-challenged males would reduce eating and drinking behaviors (as avoidance behaviors) and that their blood would show activation of immune and stress responses. We used female Japanese quail as a study system because they have been shown to respond to male traits, in terms of their own physiology and egg investment. Only two genes showed significant differential expression due to treatment, including an increase in the threonine dehydrogenase (TDH) transcript, an enzyme important for threonine breakdown. However, hundreds of genes in pathways related to activation of immune responses showed coordinated up-regulation in females exposed to immune-challenged males. Suppressed pathways revealed potential changes to metabolism and reduced responsiveness to glucocorticoids. Contrary to our prediction, we found that females paired with immune-challenged males increased food consumption. Water consumption was not changed by treatment. These findings suggest that even short exposure to diseased conspecifics can trigger both behavioral and physiological responses in healthy animals.


Assuntos
Coturnix , Transcriptoma , Animais , Masculino , Feminino , Coturnix/genética , Reprodução , Imunidade
4.
Sci Total Environ ; 855: 158902, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36152855

RESUMO

Aluminum (Al) is an abundant metal that has been classified as a threatening pollutant due to indiscriminate use and anthropogenic activities. This study aimed to evaluate the impacts of Al on crayfish (Procambarus clarkii), including biochemical change, histological alteration, gut microbial community diversification, and immune changes. The bioaccumulation of Al was detected in the hemolymph and intestine of crayfish after Al exposure at different time points. Results showed that Al exposure significantly induced oxidative stress and caused pathohistological changes on intestinal barrier structures in crayfish. It was found that the intestinal microbiota was affected by retained Al and the intestinal community diversity was changed after Al treated in the crayfish. Furthermore, Al exposure affected the immunity in crayfish, by altering the expression of a set of immune-related genes, as well as reducing the phenoloxidase and lysozyme activities. Moreover, Al exposure promoted hemocytes apoptosis and impaired hemophagocytic capacity against Vibro parahamolyticus, resulting in higher mortality of crayfish upon bacterial infection. Taken these results together, we conclude that excessive Al exposure caused adverse effects on multiple biological processes of crayfish and Al pollution is a potential threat to crayfish culture.


Assuntos
Alumínio , Astacoidea , Animais , Alumínio/toxicidade , Hemócitos , Estresse Oxidativo , Imunidade
5.
Methods Mol Biol ; 2578: 209-217, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152290

RESUMO

In SARS-CoV-2 pandemic scenario, the identification of rapid methods to detect antibodies against coronavirus has been a wide and urgent issue. Epitope mapping on peptide microarrays is a rapid way to identify sequences with a high immunoreactivity. The process begins with a proteome-wide screening, based on immune affinity; the use of a high-density microarray is followed by a validation phase, where a restricted panel of probes is tested using peptide microarrays; peptide sequences are immobilized through a click-based strategy.COVID-19-positive sera are tested and immuno-domains regions are identified on SARS-CoV-2 spike (S), nucleocapsid (N) protein, and Orf1ab polyprotein. An epitope on N protein (region 155-171) provided good diagnostic performance in discriminating COVID-19-positive vs. healthy individuals. Using this sequence, 92% sensitivity and 100% specificity are reached for IgG detection in COVID-19 samples, and no cross-reactivity with common cold coronaviruses is detected. Overall, epitope 155-171 from N protein represents a promising candidate for further development and rapid implementation in serological tests.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , COVID-19/diagnóstico , Mapeamento de Epitopos , Epitopos , Humanos , Imunidade , Imunoglobulina G , Poliproteínas , Proteoma , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus
6.
Acta Trop ; 237: 106748, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36368413

RESUMO

Giardiasis is an intestinal protozoal disease caused by Giardia lamblia (G. lamblia) which is a major worldwide health problem due to development of resistance to commonly used drugs. Therefore, it is necessary to identify an effective drug for giardiasis. This study aimed to assess the therapeutic role of L-citrulline against giardiasis in experimental animals. 40 male Swiss Albino weaned rats were used in this study, divided into four groups. Group I: normal control; group II: infected un-treated; group III: infected and treated with L-citrulline and Group IV: infected and treated with metronidazole. The efficacy was evaluated by counting Giardia trophozoites in the intestinal mucosa and cysts in the stool of infected rats. Histopathological analyses, immunohistochemistry expression of inducible nitric oxide synthase (iNOS) in the small intestine tissues were performed. Along with, serum IL6, the intestinal arginase enzyme level and giardial flavohemoglobin (flavoHb) expression were measured. L-citrulline administration reduced the mean number of G. lamblia cysts and trophozoites, serum IL-6, and intestinal arginase enzyme levels. Furthermore, the intestinal brush border was restored, with a reduction in the inflammatory infiltrate and an increase in iNOS activity. Moreover, there was a significant decrease in flavoHb gene expression in both the L-citrulline and metronidazole treated groups. Thus L-citrulline is effective in NO production therefore it has a therapeutic potential in controlling giardiasis.


Assuntos
Cistos , Giardia lamblia , Giardíase , Masculino , Camundongos , Ratos , Animais , Giardíase/tratamento farmacológico , Citrulina/farmacologia , Citrulina/uso terapêutico , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Arginase , Giardia , Trofozoítos , Arginina/farmacologia , Imunidade
7.
Acta Trop ; 237: 106749, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36370753

RESUMO

The pathogenesis of Chronic Chagas Cardiomyopathy (CCC) is still not fully understood, and the persistence of the parasite in tissues seems to be essential for the onset and progression of heart disease, tissue destruction, and chronic inflammation. It is clear that the polarity found between the asymptomatic (IND) and cardiac clinical forms refers mainly to the mechanisms involved in the regulation of the host's immune response. Thus, to elucidate aspects of the susceptibility of host phagocytes to T. cruzi infection, the present study explored novel aspects of innate immune response, integrating data on susceptibility to infection and intracellular replication, using monocyte-derived macrophages from CCC patients, together with memory CD4+ T-cells (CD45RO+). The isolation of PBMC was conducted by means of in vitro infection assay with T. cruzi trypomastigotes and flow cytometry analysis of the intracytoplasmic cytokine production by CD4+T-cells. Our findings indicated that monocytes derived from individuals with CCC are more susceptible to the infection and replication of intracellular amastigotes. Moreover, the stimulation of CD4+ T-cells from CCC patients, together with T. cruzi trypomastigotes, induces a predominance of a regulatory response over a type 1 response, demonstrated by an increase in IL-10 production and a reduction in the IFN-γ and IFN-γ/IL-10. Suppression of the function of monocyte-derived macrophages, from CCC patients, to control trypomastigote infection and intracellular replication sheds light on a potential susceptibility of these cells isolated from peripheral blood, which may reflect the ineffectiveness of parasite control by phagocytes in cardiac tissues, which can subsequently result in serious heart disease.


Assuntos
Cardiomiopatia Chagásica , Doença de Chagas , Trypanosoma cruzi , Humanos , Interleucina-10 , Leucócitos Mononucleares , Linfócitos T , Macrófagos , Imunidade
8.
Oxid Med Cell Longev ; 2022: 2644205, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35345830

RESUMO

The aim of the present study was to investigate the effects of intrauterine growth retardation (IUGR) on the intestinal morphology, intestinal epithelial cell apoptosis, intestinal antioxidant capacity, intestinal glucose absorption capacity, and intestinal barrier function of piglets during the suckling period. A total of eight normal-birth-weight (NBW) piglets and eight IUGR newborn piglets (Duroc × Landrace × Yorkshire) were selected from eight litters, one NBW and one IUGR newborn piglet per litter. In each litter, piglets with birth weight of 1.54 ± 0.04 kg (within one SD of the mean birth weight) were selected as NBW piglets and piglets with birth weight of 0.82 ± 0.03 kg (two SD below the mean birth weight) were selected as IUGR piglets. At 21 days of age, all piglets were killed by exsanguinations for sampling. The results showed the body weight (BW) of IUGR piglets on day 0, day 7, day 14, and day 21, and the body weight gain (BWG) of IUGR piglets was significantly lower than that of NBW piglets. IUGR piglets exhibited impaired intestinal morphology, raised enterocyte apoptosis, and increased oxidative damage. It showed that IUGR leads to a lower antioxidant capacity and glucose absorption in the jejunum. In accordance, IUGR caused the intestinal barrier dysfunction by impairing tight junctions and increasing intestinal inflammatory injury. Collectively, these results add to our understanding that IUGR affects intestinal health of suckling piglets via altering intestinal antioxidant capacity, glucose uptake, tight junction, and immune responses, and the slow growth of piglets with IUGR may be associated with intestinal injury.


Assuntos
Antioxidantes , Retardo do Crescimento Fetal , Animais , Glucose , Imunidade , Suínos , Junções Íntimas
9.
Cell Death Dis ; 13(10): 915, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316313

RESUMO

Acute myeloid leukemia (AML) is a rapidly progressing and often fatal hematopoietic malignancy. Venetoclax (VEN), a recent FDA-approved BCL-2 selective inhibitor, has high initial response rates in elderly AML patients, but the majority of patients eventually acquire resistance. Multiple studies have demonstrated that the female sex is associated with better outcomes in patients with AML, which are predominantly attributed to estrogen signaling. As a novel membrane estrogen receptor, G protein-coupled estrogen receptor (GPER)-mediated-rapid estrogen effects have attracted considerable attention. However, whether targeting GPER enhances the antileukemic activity of VEN is unknown. In this study, we first demonstrated that GPER expression was dramatically reduced in AML cells owing to promoter hypermethylation. Furthermore, pharmacological activation of GPER by G-1 combined with VEN resulted in synergistic antileukemic activity in vitro and in vivo. Mechanistically, G-1/VEN combination synergistically triggered concurrent mitochondria-related apoptosis and gasdermin E (GSDME)-dependent pyroptosis by activating p38-MAPK/myeloid cell leukemia 1 (MCL-1) axis. Importantly, leukemic pyroptosis heightened CD8+ T cell immune function by releasing interleukin (IL)-1ß/18 into the tumor microenvironment. Our study corroborates that GPER activation shows a synergistic antileukemic effect with VEN, making it a promising therapeutic regimen for AML.


Assuntos
Leucemia Mieloide Aguda , Receptores de Estrogênio , Humanos , Feminino , Idoso , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Piroptose , Linhagem Celular Tumoral , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Leucemia Mieloide Aguda/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Estrogênios , Imunidade , Microambiente Tumoral
10.
Nat Commun ; 13(1): 6534, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319625

RESUMO

Cancer vaccine, which can promote tumor-specific immunostimulation, is one of the most important immunotherapeutic strategies and holds tremendous potential for cancer treatment/prevention. Here, we prepare a series of nanoparticles composed of doxorubicin- and tyrosine kinase inhibitor-loaded and hyaluronic acid-coated dendritic polymers (termed HDDT nanoparticles) and find that the HDDT nanoparticles can convert various cancer cells to micrometer-sized vesicles (1.6-3.2 µm; termed HMVs) with ~100% cell-to-HMV conversion efficiency. We confirm in two tumor-bearing mouse models that the nanoparticles can restrain tumor growth, induce robust immunogenic cell death, and convert the primary tumor into an antigen depot by producing HMVs in situ to serve as personalized vaccines for cancer immunotherapy. Furthermore, the HDDT-healed mice show a strong immune memory effect and the HDDT treatment can realize long-term protection against tumor rechallenge. Collectively, the present work provides a general strategy for the preparation of tumor-associated antigen-containing vesicles and the development of personalized cancer vaccines.


Assuntos
Vacinas Anticâncer , Nanopartículas , Neoplasias , Camundongos , Animais , Células Dendríticas , Imunoterapia , Antígenos de Neoplasias , Neoplasias/tratamento farmacológico , Imunidade
11.
Cancer Discov ; 12(11): 2496-2497, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36321309

RESUMO

Martini and colleagues performed genetic ancestry estimation on a unique international triple-negative breast cancer (TNBC) study enriched for participants with African ancestry. They identified gene signatures indicative of ancestry in race-associated TNBC and found ancestry-associated immunologic differences that may contribute to racial disparities in breast cancer. See related article by Martini et al., p. 2530 (5).


Assuntos
Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Transcriptoma , Imunidade , Biologia
12.
Front Immunol ; 13: 999233, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341352

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-19 (COVID-19). The spike protein (S) of SARS-CoV-2 plays a crucial role in mediating viral infectivity; hence, in an extensive effort to curb the pandemic, many urgently approved vaccines rely on the expression of the S protein, aiming to induce a humoral and cellular response to protect against the infection. Given the very limited information about the effects of intracellular expression of the S protein in host cells, we aimed to characterize the early cellular transcriptomic changes induced by expression of the S protein in THP-1-derived macrophage-like cells. Results showed that a wide variety of genes were differentially expressed, products of which are mainly involved in cell adhesion, homeostasis, and most notably, antiviral and immune responses, depicted by significant downregulation of protocadherins and type I alpha interferons (IFNAs). While initially, the levels of IFNAs were higher in the medium of S protein expressing cells, the downregulation observed on the transcriptomic level might have been reflected by no further increase of IFNA cytokines beyond the 5 h time-point, compared to the mock control. Our study highlights the intrinsic pathogenic role of the S protein and sheds some light on the potential drawbacks of its utilization in the context of vaccination strategies.


Assuntos
COVID-19 , Interferon Tipo I , Humanos , Glicoproteína da Espícula de Coronavírus , SARS-CoV-2 , Antivirais/farmacologia , Protocaderinas , Imunidade , Macrófagos/metabolismo
13.
Molecules ; 27(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36364137

RESUMO

Helicobacter pylori is a Gram-negative, microaerophilic, curved-rod, flagellated bacterium commonly found in the stomach mucosa and associated with different gastrointestinal diseases. With high levels of prevalence worldwide, it has developed resistance to the antibiotics used in its therapy. Brazilian red propolis has been studied due to its biological properties, and in the literature, it has shown promising antibacterial activities. The aim of this study was to evaluate anti-H. pylori from the crude hydroalcoholic extract of Brazilian red propolis (CHEBRP). For this, in vitro determination of the minimum inhibitory and bactericidal concentration (MIC/MBC) and synergistic activity and in vivo, microbiological, and histopathological analyses using Wistar rats were carried out using CHEBRP against H. pylori strains (ATCC 46523 and clinical isolate). CHEBRP presented MIC/MBC of 50 and 100 µg/mL against H. pylori strains (ATCC 43526 and clinical isolate, respectively) and tetracycline MIC/MBC of 0.74 µg/mL. The association of CHEBRP with tetracycline had an indifferent effect. In the stomach mucosa of rats, all treatments performed significantly decreased the number of H. pylori, and a concentration of 300 mg/kg was able to modulate the inflammatory response in the tissue. Therefore, CHEBRP showed promising anti-H. pylori in in vitro and in vivo assays.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Própole , Ratos , Animais , Própole/farmacologia , Própole/uso terapêutico , Brasil , Ratos Wistar , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Imunidade , Tetraciclinas/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia
14.
Cells ; 11(21)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36359764

RESUMO

BACKGROUND: Intestinal ischemia and reperfusion (IRI) injury induces acute and long-lasting damage to the neuromuscular compartment and dysmotility. This study aims to evaluate the pathogenetic role of hyaluronan (HA), a glycosaminoglycan component of the extracellular matrix, as a modulator of the enteric neuronal and immune function and of the colonic microbiota during in vivo IRI in the rat small intestine. METHODS: mesenteric ischemia was induced in anesthetized adult male rats for 60 min, followed by 24 h reperfusion. Injured, sham-operated and non-injured animals were treated with the HA synthesis inhibitor, 4-methylumbelliferone (4-MU 25 mg/kg). Fecal microbiota composition was evaluated by Next Generation Sequencing. Neutrophil infiltration, HA homeostasis and toll like receptor (TLR2 and TLR4) expression in the small intestine were evaluated by immunohistochemical and biomolecular approaches (qRT-PCR and Western blotting). Neuromuscular responses were studied in vitro, in the absence and presence of the selective TLR2/4 inhibitor, Sparstolonin B (SsnB 10, 30 µM). RESULTS: 4-MU significantly reduced IRI-induced enhancement of potentially harmful Escherichia and Enterococcus bacteria. After IRI, HA levels, neutrophil infiltration, and TLR2 and TLR4 expression were significantly enhanced in the muscularis propria, and were significantly reduced to baseline levels by 4-MU. In the injured, but not in the non-injured and sham-operated groups, SsnB reduced both electrical field-stimulated (EFS, 0.1-40 Hz) contractions and EFS-induced (10 Hz) non-cholinergic non-adrenergic relaxations. CONCLUSIONS: enhanced HA levels after intestinal IRI favors harmful bacteria overgrowth, increases neutrophil infiltration and promotes the upregulation of bacterial target receptors, TLR2 and TLR4, in the muscularis propria, inducing a pro-inflammatory state. TLR2 and TLR4 activation may, however, underlay a provisional benefit on excitatory and inhibitory neuronal pathways underlying peristalsis.


Assuntos
Microbiota , Traumatismo por Reperfusão , Animais , Masculino , Ratos , Ácido Hialurônico/metabolismo , Imunidade , Intestino Delgado/metabolismo , Traumatismo por Reperfusão/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo
15.
Front Immunol ; 13: 1012459, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341336

RESUMO

NLRC3 is a member of the pattern recognition receptors nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) family, and plays a pivotal regulatory role in modulating the activation of immune cells. In macrophages, NLRC3 inhibits the activation of the NF-κB signaling pathway, the STING/TBK1 signaling pathway, and the formation of the inflammasome. In the context of T cells immune response, NLRC3 prevents the activation of T cells by regulating the function of dendritic cells and directly influencing the function of T cells. Different from other pattern recognition receptors, NLRC3 is more closely associated with regulatory activity than pathogens recognition, it influences the fates of cells, for example, prevents proliferation, promotes apoptosis and inhibits pyroptosis. These cellular functions regulated by NLRC3 are involved in the development processes of a variety of diseases, such as infectious disease, sterile inflammatory diseases, and cancer. However, its characteristics, function and regulatory mechanism in immune response and immune-related diseases have not been addressed fully. In this review, we elaborate the potential roles of NLRC3 from several different levels, include molecular mechanism, cellular functions in the immune-related diseases.


Assuntos
Inflamassomos , Peptídeos e Proteínas de Sinalização Intercelular , Inflamassomos/metabolismo , Imunidade , Transdução de Sinais , Receptores de Reconhecimento de Padrão
16.
Front Immunol ; 13: 1021556, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341449

RESUMO

Livestock animals, such as swine, are an important source of Toxoplasma gondii in the human population. Currently, there is limited knowledge regarding the potential influence that the T. gondii genotype might exert on establishing infection in swine. Herein, we investigated the role of 2 T. gondii isolates, type II and III, representative of the genotypes circulating in Europe, in the immune responses and infection dynamics in piglets. Recently obtained oocysts (103) from the T. gondii field isolates TgShSp1 (type II, ToxoDB genotype #3) and TgShSp24 (type III, #2) were used for oral infection. Thirteen 50-day-old female piglets of the Landrace-Large White crossbreed were randomly allocated into three different groups: Group 1 (G1, n=5), inoculated with TgShSp1; Group 2 (G2, n=5), inoculated with TgShSp24; and Group 3 (G3, n=3), a non-infected control group. Clinical signs were monitored daily until 42 days post-infection (dpi) when piglets were euthanized. Blood samples were collected weekly to test the cellular immune response in parasite-stimulated peripheral blood and specific IgG, IgG1 and IgG2, responses in sera. Parasite distribution and burden were evaluated in target tissues using a mouse bioassay and quantitative RT-PCR (qPCR). Apathy and a moderate decrease in feed consumption were observed in G1 and G2 piglets between 5 and 8 dpi, coinciding with fever (>40°C). G2 piglets had higher temperatures for a longer duration. Using mouse bioassay and qPCR, the detection frequency was higher in G2 vs. G1, and the highest parasite burdens in target tissues were also found in G2. Seroconversion was detected at 14 dpi in both infected groups, but higher antibody levels were observed in G2 piglets. Cytokine analyses revealed the production of IL-8, IL-1ß and IFN-ɤ from 7 dpi in both infected groups. Moreover, IL-12 was produced from 7 dpi in G1 and from 14 dpi in G2. Levels of IL-8 were higher in G2, but IL-1ß, IL-12 and IFN-ɤ were higher in G1 at 14 dpi. This cytokine profile reveals a predominant proinflammatory response that could be involved in limiting T. gondii infection in piglets, although it is more efficient against TgShSp1 type II-driven infection.


Assuntos
Toxoplasma , Toxoplasmose Animal , Animais , Feminino , Imunidade , Imunoglobulina G , Interleucina-12 , Interleucina-8 , Oocistos , Suínos
17.
Biomed Res Int ; 2022: 4740686, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36349315

RESUMO

Background: Biological processes serve crucial functions in the initiation and development of cancer. Therefore, we constructed and validated a model for bladder cancer (BLCA) with good predictive power for immunity, prognosis, and therapy. Methods: Using the expression of the gene sets based on biological processes, BLCA patients were divided into three clusters by consensus cluster analysis. By performing LASSO regression analysis twice, key genes were selected, and the biological processes-related genes' (BPRG) score was calculated. Differences in immune infiltration, tumor microenvironment, tumor mutation burden, immunotherapy, and sensitivity towards chemotherapy were analyzed between two groups divided by BPRG score. Results: Good accuracy was observed for the three clusters. They showed different prognoses and levels of immune cell infiltration. The selected key genes were mainly enriched in immune-related pathways. The high-BPRG score group was related to poor prognosis, higher immune cell infiltration, interstitial scores, and increased tumor mutation. Moreover, the effects of immunotherapy were good, and those of chemotherapy were poor. Conclusion: Overall, key genes may be involved in various complex immune regulation processes. Therefore, the quantification and verification of the BPRG score are expected to facilitate the understanding of the immunosuppressive microenvironment in BLCA and guide the choice of chemotherapeutic drugs and immunotherapeutic regimens and help predict the prognoses of patients with BLCA.


Assuntos
Fenômenos Biológicos , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Perfilação da Expressão Gênica , Prognóstico , Imunidade , Microambiente Tumoral/genética
19.
Zhonghua Jie He He Hu Xi Za Zhi ; 45(11): 1146-1152, 2022 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-36344232

RESUMO

Tuberculosis (TB) is a chronic infectious disease caused by mycobacterium tuberculosis (MTB) infection. Macrophages are the first line in defensing MTB infection and the main host cells for the growth and persistence of MTB. Changes in macrophage function are critical for the host response to tuberculosis. Non-coding RNAs are involved in the pathophysiological process of many diseases, including TB, and play a very important regulatory role in the macrophage mediated immune response process. Therefore, we reviewed the mechanisms of the non-coding RNAs mediated function alteration of macrophages, in order to facilitate identification of potential therapeutic targets for host-directed anti-TB treatment.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Tuberculose/microbiologia , Macrófagos/microbiologia , Imunidade
20.
Viruses ; 14(11)2022 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-36366425

RESUMO

Oncolytic viruses (OVs) can specifically replicate in the host and cause cancer cell lysis while inducing an antitumor immune response. The aim of this study is to investigate the impact of either pre-existing immunity against herpes simplex virus type-1 (HSV-1) or multicycle treatment with OVs on anticancer efficacy of VG161, an HSV-1 OV in phase 2 clinical trial. VG161 efficacy was tested in CT26 mouse models by comparing the efficacy and immune response in naïve mice or in mice that were immunized with VG161. Moreover, VG161 efficacy in HLA-matched CD34+ humanized intrahepatic cholangiocarcinoma (ICC) patient-derived xenograft (PDX) models was also tested in multicycle treatment and was compared to standard chemotherapy for this type of cancer (gemcitabine). The HSV-1-immunized mice significantly inhibited tumor growth in VG161-treated mice compared to control naïve treated mice. RNA expression profiling and ELISPOT analyses indicated changes in the tumor's immune profile in the immunized and treated group compared to naïve and treated mice, as well as enhanced T cell function depicted by higher numbers of tumor specific lymphocytes, which was enhanced by immunization. In the ICC PDX model, repeated treatment of VG161 with 2 or 3 cycles seemed to increase the anticancer efficacy of VG161. In conclusion, the anticancer efficacy of VG161 can be enhanced by pre-immunization with HSV-1 and multicycle administration when the virus is given intratumorally, indicating that pre-existing antiviral immunity might enhance OV-induced antitumor immunity. Our results suggest potential clinical benefits of HSV-1-based OV therapy in HSV-1-seropositive patients and multicycle administration of VG161 for long-term maintenance treatment.


Assuntos
Herpesvirus Humano 1 , Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Camundongos , Animais , Vírus Oncolíticos/fisiologia , Herpesvirus Humano 1/genética , Neoplasias/terapia , Imunidade , Modelos Animais de Doenças , Terapia Viral Oncolítica/métodos
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