Nonpathogenic SIV and Pathogenic HIV Infections Associate with Disparate Innate Cytokine Signatures in Response to M. bovis BCG
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ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE81926
PROVIDER: PRJNA323449 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Infections with mycobacteria, including Mycobacterium tuberculosis (Mtb) and Mycobacterium bovis (M. bovis) BCG, are a leading cause of morbidity and mortality for HIV-infected persons. In contrast to HIV, SIV infection of sooty mangabeys is nonpathogenic, characterized by a lack of clinical disease including an absence of opportunistic infections. The goal of this study was to identify innate immune responses to M. bovis BCG maintained during nonpathogenic lentiviral infections, through a comparison of functional responses during pathogenic HIV or nonpathogenic SIV infections. Monocytes were evaluated for their ability to express key anti-mycobacterial cytokines TNF-α and IL-12 following a six-hour ex vivo BCG exposure. While HIV-infection was associated with a decreased percentage of IL-12-producing monocytes, nonpathogenic SIV-infection was associated with an increased percentage of monocytes producing both cytokines. Gene expression analysis of PBMC following ex vivo BCG exposure identified differential expression of NK cell-related genes and several cytokines, including IFN-γ and IL-23, between HIV-infected and control subjects. In contrast, SIV-infected and uninfected-control mangabeys exhibited no significant differences in gene expression after BCG exposure. Finally, differential gene expression patterns were identified between species, with mangabeys exhibiting lower IL-6 and higher IL-17 in response to BCG when compared to humans. Overall, this comparison of immune responses to M. bovis BCG identified unique immune signatures (involving cytokines IL-12, TNF-α, IL-23, IL-17, and IL-6) that are altered during HIV, but maintained or increased during nonpathogenic SIV infections. These unique cytokine and transcriptome signatures provide insight into the differential immune responses to Mycobacteria during pathogenic HIV-infection of humans or nonpathogenic SIV-infection of mangabeys.
2016-05-27 | GSE81926 | GEO
Project description:Infections with mycobacteria, including Mycobacterium tuberculosis (Mtb) and Mycobacterium bovis (M. bovis) BCG, are a leading cause of morbidity and mortality for HIV-infected persons. In contrast to HIV, nonpathogenic SIV infections of sooty mangabeys are characterized by a lack of clinical disease including an absence of opportunistic infections. The goal of this study was to identify innate immune responses to M. bovis BCG maintained during nonpathogenic lentiviral infections through a comparison of functional responses during pathogenic HIV or nonpathogenic SIV infections. Monocytes were evaluated for their ability to express key anti-mycobacterial cytokines TNF-α and IL-12 following a six-hour ex vivo BCG exposure. While HIV-infection was associated with a decreased percentage of IL-12-producing monocytes, nonpathogenic SIV-infection was associated with an increased percentage of monocytes producing both cytokines. Gene expression analysis of PBMC following ex vivo BCG exposure identified differential expression of NK cell-related genes and several cytokines, including IFN-γ and IL-23, between HIV-infected and control subjects. In contrast, SIV-infected and uninfected-control mangabeys exhibited no significant differences in gene expression after BCG exposure. Finally, differential gene expression patterns were identified between species, with mangabeys exhibiting lower IL-6 and higher IL-17 in response to BCG when compared to humans. Overall, this comparison of immune responses to M. bovis BCG identified unique immune signatures (involving cytokines IL-12, TNF-α, IL-23, IL-17, and IL-6) that are altered during HIV, but maintained or increased during nonpathogenic SIV infections. These unique cytokine and transcriptome signatures provide insight into the differential immune responses to Mycobacteria during pathogenic HIV-infection that may be associated with an increased incidence of mycobacterial co-infections.
| S-EPMC4978473 | biostudies-literature
Project description:To find the differences in innate immune response between nonpathogenic and pathogenic SIV infection, we examined transcriptome in PBMCs from macaques infected with pathogenic or nonpathogenic SIV.
2014-10-10 | GSE62209 | GEO
Project description:To find the differences in innate immune response between nonpathogenic and pathogenic SIV infection, we examined transcriptome in PBMCs from macques infected with pathogenic or nonpathogenic SIV. Juvenile macaques were intavenousy infected with SIVmac239 or M-bM-^HM-^F5G. Blood samples were collected at 1 week and 3 weeks pi. Total RNA from the PBMCs were used for the microarray analysis.
2014-10-10 | E-GEOD-62209 | biostudies-arrayexpress
Project description:HIV cure efforts are increasingly focused on harnessing CD8 T cell functions; however, a deeper understanding of CD8 T cells promoting HIV control is necessary to properly inform therapeutic approaches. Here, we identified a novel TOX-expressing CD8 T cell population associated with control of SIV infection in lymphoid tissue of rhesus macaques defined as an antigen-responsive TCF1+ CD39+ subset expressing high levels of TOX and inhibitory receptors but lower levels of canonical cytolytic molecules such as granzyme B, granzyme A, and perforin. Transcriptional analysis of SIV-specific CD8 T cells, as well as proteomic analysis of purified CD8 T cell subsets, revealed these TCF1+ CD39+ cells as an intermediate effector population retaining stem-like features while maintaining a lineage relationship with terminal effector cells. TCF1+ CD39+ CD8 T cells expressed higher levels of CXCR5 than terminally differentiated cells, were found at higher frequency in follicular micro-environments, and were preferentially located in the proximity of SIV-RNA+ cells both in lymph node T cell zone and B cell follicles. Importantly, their frequency was strongly associated with reduced plasma viremia and lower reservoir size. Finally, we confirmed the presence of a highly similar TOX-enriched TCF1+ CD39+ cell population in lymph node biopsies from ART-naïve and ART-treated people living with HIV. Collectively, these data identify a unique population of lymphoid CD8 T cells possessing both stem-like and effector properties that contribute to limiting HIV/SIV persistence.
2024-06-11 | PXD050498 | Pride
Project description:The molecular mechanisms underlying HIV-induced inflammation remain incompletely defined although they associate with morbidity and progression to AIDS. Here we used non-human primate models of pathogenic and nonpathogenic simian immunodeficiency virus (SIV) infection in respectively macaques and African green monkeys. We longitudinally analyzed DNA methylation changes in CD4+ T cells from lymph node and blood using species-compatible probes on human 450K methylation BeadArrays. Selected identified sites were validated using bisulfite-pyrosequencing of an independent cohort of uninfected, viremic and SIV controller macaques. Tissue- and species-specific DNA methylation changes were observed after SIV infection. The most affected genes in pathogenic SIV infection were related to metabolic pathways and Th1 signaling. SIV-infected macaques displayed increased insulin sensitivity early in the chronic phase of infection, which correlated with T cell activation. Moreover, DNA methylation changes in the Th1 pathway were associated with altered gene expression. Out of the 11 selected genes for validation, six genes showed differential methylation in viremic and uninfected macaques. In contrast, no significant differences were found between uninfected and SIV-controller macaques. In summary, pathogenic SIV infection associates with DNA methylation changes in genes related to metabolism and immune-regulation.
2020-12-15 | GSE143708 | GEO
Project description:Mycobacterial Ser/Thr kinases play a critical role in bacterial physiology and pathogenesis. Linking kinases to the substrates they phosphorylate in vivo, thereby elucidating their exact functions, is still a challenge. The aim of this work was to associate protein phosphorylation in mycobacteria with important subsequent macro cellular events by identifying the physiological substrates of PknG in Mycobacterium bovis BCG. The study compared the phosphoproteome dynamics during the batch growth of M. bovis BGC versus the respective PknG knock-out mutant (ΔPknG-BCG) strains.
2018-03-23 | PXD006473 | Pride
Project description:Distinct SIV-specific lymphoid tissue CD8 T cells exhibit simultaneous effector and stem-like profiles and associate with limited SIV persistence
| PRJNA1107615 | ENA
Project description:Some viruses have established an equilibrium with their host. African green monkeys (AGM) display persistent high viral replication in blood and intestine during Simian immunodeficiency virus (SIV) infection but resolve systemic inflammation after acute infection and lack intestinal immune or tissue damage during chronic infection. We show that NKG2 a/c + CD8 + T cells increase in blood and intestine of AGM in response to SIVagm infection in contrast to SIVmac infection in macaques, the latter modeling HIV infection. NKG2 a/c + CD8 + T cells were not expanded in lymph nodes and CXCR5 + NKG2 a/c + CD8 + T cell frequencies further decreased after SIV infection. Genome-wide transcriptome analysis of NKG2 a/c + CD8 + T cells from AGM revealed the expression of NK cell receptors, and of molecules with cytotoxic effector, gut homing, immunoregulatory and gut barrier function, including CD73. NKG2 a/c + CD8 + T cells correlated negatively with IL-23 in the intestine during SIVmac infection. The data suggest a potential regulatory role of NKG2 a/c + CD8 + T cells in intestinal inflammation during SIV/HIV infections.
2021-03-11 | E-MTAB-8664 | biostudies-arrayexpress
Project description:HIV cure efforts are increasingly focused on harnessing CD8 T cell functions; however, a deeper understanding of CD8 T cells promoting HIV control is necessary to properly inform therapeutic approaches. Here, we identified a novel TOX-expressing CD8 T cell population associated with control of SIV infection in lymphoid tissue of rhesus macaques defined as an antigen-responsive TCF1+ CD39+ subset expressing high levels of TOX and inhibitory receptors but lower levels of canonical cytolytic molecules such as granzyme B, granzyme A, and perforin. Transcriptional analysis of SIV-specific CD8 T cells, as well as proteomic analysis of purified CD8 T cell subsets, revealed these TCF1+ CD39+ cells as an intermediate effector population retaining stem-like features while maintaining a lineage relationship with terminal effector cells. TCF1+ CD39+ CD8 T cells expressed higher levels of CXCR5 than terminally differentiated cells, were found at higher frequency in follicular micro-environments, and were preferentially located in the proximity of SIV-RNA+ cells both in lymph node T cell zone and B cell follicles. Their frequency was strongly associated with reduced plasma viremia and, importantly, lower size of the intact reservoir. Finally, we confirmed the presence of a highly similar TOX-enriched TCF1+ CD39+ cell population in lymph node biopsies from ART-naïve and ART-treated people living with HIV. Collectively, these data identify a unique population of lymphoid CD8 T cells possessing both stem-like and effector properties that contribute to limiting HIV/SIV persistence.
2024-05-29 | GSE266576 | GEO