HIV-associated gut microbiome regulates intestinal intra-epithelial lymphocytes and opportunistic infection
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB81733 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Maternal intra-epithelial lymphocytes support lactogenesis and offspring fitness
| PRJNA1068069 | ENA
Project description:Mammary intra-epithelial lymphocytes promote lactogenesis and offspring fitness
| PRJNA1175826 | ENA
Project description:Breastfeeding is an obligatory requirement of mammalian survival. This fundamental process is associated with the remodeling of maternal physiology including the transformation of mammary gland into milk-secreting organ. While adaptive immunity has been associated with the broad control of host physiology, how maternal immunity contributes to organismal remodeling during pregnancy including mammary gland remodeling and function remains largely unknown. Here, we show that maternal adaptive immunity plays a critical role in shaping lactogenesis. Specifically, physiological adaptation to pregnancy is associated with thymic involution and paradoxical enrichment in intraepithelial lymphocyte precursors that no longer migrate to the gut but preferentially accumulate within the mammary gland. Within this compartment the precursors develop as T-bet expressing lymphocytes accumulating within the mammary epithelium in an IL-15 dependent manner. Mammary intra-epithelial lymphocytes control milk production by favoring differentiation of both contractile and milk-secreting cells, thereby affecting offspring fitness. Altogether, this work uncovers a previously unappreciated contribution of the maternal adaptive immune system in organismal remodeling during pregnancy associated with mammary gland development and function.
2025-02-14 | GSE253989 | GEO
Project description:Breastfeeding is an obligatory requirement of mammalian survival. This fundamental process is associated with the adaptation of maternal physiology including the transformation of the mammary gland into a milk-secreting organ. How maternal immunity contributes to mammary gland remodeling and function remains largely unknown. Here, we show that maternal adaptive immunity plays a critical role in shaping lactogenesis. Specifically, physiological adaptation during pregnancy is associated with thymic involution and a paradoxical enrichment in intraepithelial lymphocyte (IEL) precursors that no longer migrate to the gut, but instead preferentially accumulate within the mammary gland. Within this compartment, IEL precursors differentiate into T-bet-expressing unconventional CD8 lymphocytes with a cytotoxic signature which accumulate within the mammary epithelium in an IL-15-dependent manner. Mammary intra-epithelial lymphocytes control milk production by favoring differentiation and maturation of both contractile and milk-secreting cells, thereby promoting offspring fitness. Altogether, this work uncovers a previously unappreciated contribution of the maternal adaptive immune system in organismal remodeling during pregnancy that is associated with mammary gland development and function.
2025-06-04 | GSE280020 | GEO
Project description:The study recapitulates, through in vitro micropatterned co-cultures, interactions between HIV-infected T-lymphocytes and intestinal epithelial cells in order to investigate the mechanisms underlying the disruption of normal epithelial cell and barrier function during HIV infection. The co-culture method simplifies observation/monitoring of the two cell types and is particularly suited for laser microdissection-based retrieval of the epithelial cells for downstream gene expressions studies. Microarrays were used to characterize changes in gene expression in HT29 epithelial cells co-cultured with Jurkat T-lymphocytes in the presence and absence of HIV infection Micropatterned co-cultures were generated of healthy or HIV-infected T-lymphocytes (Jurkat) and human intestinal epithelial (HT-29) cells whereby both cell types were positioned on the same surface in a price spatial configuration (micropattern). HT29 celsl were then isolated by laser capture microdissection and used for RNA extraction and hybridization on Affymetrix U133 Plus2 microarrays.
2014-03-22 | E-GEOD-56090 | biostudies-arrayexpress
Project description:Assessment of the extent to which the altered profiles of miRNA expression influence viral replication and latency, as well as the efficiency of host defenses, may be useful for understanding the basis of the HIV-1-related alterations in cellular physiology and immunologic control. To this end, three patient groups were enrolled. One group consisted of subjects who were classified as M-CM-)lite control long-term non-progressors (M-CM-)LTNP). A second study group was HIV-1-positive subjects, who were antiretroviral therapy naive. A third group was multiply exposed to HIV-1, but uninfected (MEU). This study allowed us to investigate the existence of a CD4+T- lymphocytes miRNAs signature able to discriminate among different stages of HIV-1 infection, and to evaluate whether the exposure to HIV-1 antigen is sufficient to change the miRNA profile. MicroRNAs inhibit HIV-1 expression by either modulating host innate immunity or by directly interfering with viral mRNAs. We evaluated the expression of 377 miRNAs in CD4+ T cells from HIV-1 M-CM-)lite LTNP (M-CM-)LTNP), naive and multiply exposed uninfected individuals (MEU) and we observed that the M-CM-)LTNP patients clustered with naive, whereas all MEU subjects grouped together. The discriminatory power of miRNAs showed that 21 miRNAs significantly differentiated M-CM-)LTNP from MEU and 23 miRNAs distinguished naive from MEU, while only 1 (miR-155) discriminated M-CM-)LTNP from naive. We proposed that miRNA expression may discriminate between HIV-1 infected and exposed but negative individuals. Analysis of miRNAs expression after exposure of healthy CD4+T cells to gp120 in vitro confirmed our hypothesis that a miRNA profile could be the result not only of a productive infection, but also of the exposure to HIV-1 products that leave a signature in immune cells. The comparison of normalized Dicer and Drosha expression in ex vivo and in vitro conditions revealed that these enzymes did not affect the change of miRNA profiles, supporting the existence of a Dicer-independent biogenesis pathway. We have compared miRNA profiles of CD4+ T-lymphocytes from 18 HIV-1-exposed subjects with healthy CD4+ T-lymphocytes following exposure to gp120 using a RT-qPCR assay.
2011-11-08 | E-GEOD-33514 | biostudies-arrayexpress
Project description:The study recapitulates, through in vitro micropatterned co-cultures, interactions between HIV-infected T-lymphocytes and intestinal epithelial cells in order to investigate the mechanisms underlying the disruption of normal epithelial cell and barrier function during HIV infection. The co-culture method simplifies observation/monitoring of the two cell types and is particularly suited for laser microdissection-based retrieval of the epithelial cells for downstream gene expressions studies. Microarrays were used to characterize changes in gene expression in HT29 epithelial cells co-cultured with Jurkat T-lymphocytes in the presence and absence of HIV infection
2014-03-22 | GSE56090 | GEO
Project description:The high mutation rate of HIV is linked to the generation of viruses expressing proteins with altered function whose impact on disease progression is unknown. We investigated the effects of HIV-1 viruses lacking Env, Vpr and Nef on CD4+ T cell gene expression using high-density DNA microarray analysis and functional assays. Experiment Overall Design: Human activated CD4+ T-lymphocytes from three independent donors were infected with HIV-1 viruses that lack Env and Nef (pNL4-3.eGFP.R+E- or HIVD2GFP) or Env, Vpr and Nef. (pNL4-3.eGFP.R-E- or HIVD3GFP) were pseudotyped with VSVG envelope. As a control, CD4+ T-lymphocytes were infected with VSVG-pseudotyped eGFP. CD4+ T-cells were sorted 48 hours after infection using GFP as a marker of infectivity. RNA was isolated 10 hours after sorting, labeled, and prepared for microarray analysis.
2008-10-26 | E-GEOD-12963 | biostudies-arrayexpress
Project description:HIV-1 infections of women are mainly acquired through female reproductive tract where cervical and vaginal epithelial cells are the first line of defense. Although HIV-1 does not directly infect epithelial cells, HIV-1 obligatorily interacts with and crosses over epithelial layer to infect susceptible target cells, mainly CD4+ T cells, in the lamina propria to initiate an infection. However, the mechanism and ramification of the interaction of HIV-1 and epithelial cells in vaginal transmission of HIV-1 remain to be elucidated. We hypothesized that cervical epithelial cells are not a passive barrier, but actively respond to HIV-1 to change mucosal milieu and facilitate HIV-1 transmission. We tested this hypothesis by studying the responses of cervical epithelial cells to HIV-1 through profiling genome-wide transcription. We found 1) cervical epithelial cells actively respond to HIV-1. Five hundred forty-three transcripts/genes in cervical epithelial cells were significantly altered in expression at four hours post exposure to HIV-1, of which many relate to important signaling pathways, such as innate immune responses, pattern recognition receptors, apoptosis, biosynthesis, and energy production, 2) HIV-1 increases the expression of CXC Chemokines (IL-8, CXCL1 and CXCL3) in cervical epithelial cells. IL-8 and CXCL1 are potent chemotactic for multinuclear neutrophils (MNP), monocytes and a minority of lymphocytes, and CXCL3 is predominant chemotactic for monocytes, 3) HIV-1 increases the expression of key inflammatory enzymes-COX-1 and COX-2. COX-1 is responsible for the production of prostaglandins that are important for homeostatic functions, and COX-2 is a key enzyme to convert arachidonic acid to prostaglandins, key inflammatory mediators, and 4) the increased expression of IL-8 and COX-2 revealed using microarray analysis was mapped into the endocervical epithelial cells of macaques inoculated with inactivated SIV in vivo. Our date lead to a role model of epithelial cells in HIV-1 vaginal transmission, that is the axis of HIV-1, epithelial cells, proinflammatory molecules (IL-8, CXCL1, CXCL3, COX-1 and COX-2), cell recruitment (MNP, monocytes and T cells), and inflammation. This model implies that moderating epithelial proinflammatory response to HIV-1 may be utilized in prevention of HIV vaginal transmission. Human endocervical epithelial cell line, CRL-2615, was inoculated with HIV-1 ME1 and collected 4hrs post exposure. Biologically duplicated mRNAs were prepared after exposure.
2013-02-01 | E-GEOD-42291 | biostudies-arrayexpress
Project description:Assessment of the extent to which the altered profiles of miRNA expression influence viral replication and latency, as well as the efficiency of host defenses, may be useful for understanding the basis of the HIV-1-related alterations in cellular physiology and immunologic control. To this end, three patient groups were enrolled. One group consisted of subjects who were classified as élite control long-term non-progressors (éLTNP). A second study group was HIV-1-positive subjects, who were antiretroviral therapy naive. A third group was multiply exposed to HIV-1, but uninfected (MEU). This study allowed us to investigate the existence of a CD4+T- lymphocytes miRNAs signature able to discriminate among different stages of HIV-1 infection, and to evaluate whether the exposure to HIV-1 antigen is sufficient to change the miRNA profile. MicroRNAs inhibit HIV-1 expression by either modulating host innate immunity or by directly interfering with viral mRNAs. We evaluated the expression of 377 miRNAs in CD4+ T cells from HIV-1 élite LTNP (éLTNP), naive and multiply exposed uninfected individuals (MEU) and we observed that the éLTNP patients clustered with naive, whereas all MEU subjects grouped together. The discriminatory power of miRNAs showed that 21 miRNAs significantly differentiated éLTNP from MEU and 23 miRNAs distinguished naive from MEU, while only 1 (miR-155) discriminated éLTNP from naive. We proposed that miRNA expression may discriminate between HIV-1 infected and exposed but negative individuals. Analysis of miRNAs expression after exposure of healthy CD4+T cells to gp120 in vitro confirmed our hypothesis that a miRNA profile could be the result not only of a productive infection, but also of the exposure to HIV-1 products that leave a signature in immune cells. The comparison of normalized Dicer and Drosha expression in ex vivo and in vitro conditions revealed that these enzymes did not affect the change of miRNA profiles, supporting the existence of a Dicer-independent biogenesis pathway.
2011-11-08 | GSE33514 | GEO