Elucidating human female genital tract resident DC response to HIV-1 exposure.
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PROVIDER: PRJNA1174233 | ENA |
REPOSITORIES: ENA
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Project description:The female genital tract (FGT) represents a complex and dynamic environment with specialized immune mechanisms uniquely designed to maintain a delicate balance between protection against invading pathogens and accommodating the unique physiological changes associated with reproductive function. Dendritic cells (DCs) are critical in shaping mucosal immunity against pathogens and maintaining tissue homeostasis. The unique ability of DCs to recognize invading pathogens through pattern recognition receptors (PRRs), and prime naive T cell function, make DCs ideal targets for vaccination and therapeutic strategies against cancers and infections. However, in HIV pathogenesis, DCs are considered a double-edged sword due to their ability to secrete anti-viral proteins and resist viral replication but capture and transfer active viral particles to target CD4+ T cells. Understanding the heterogeneity of DC populations in the FGT, along with their unique contribution to HIV pathogenesis is key for targeted interventions.
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Project description:Surveillance and defense of the enormous mucosal interface with the nonsterile world is critical to protecting the host from a wide range of pathogens. Chlamydia trachomatis (Ct) is an intracellular bacterial pathogen that replicates almost exclusively in the epithelium of the reproductive tract. The fallopian tubes and vagina seem poorly suited to surveillance and defense as they have limited immune infrastructure positioned near the epithelium. However, a dynamic process during clearing primary infections leaves behind new immune infrastructure positioned near epithelium. Memory lymphocyte clusters (MLC) harboring tissue resident memory T cells (TRM) are presumed to play an important role in protection from subsequent infections. Histologically Chlamydia MLC appear to be based on B cells. We therefore investigated B cell populations in the murine genital tract post-clearance of C. muridarum infections and the nature of T cells recovered from immune mice using immune B cells as antigen presenting cells (APC). These studies revealed a plasma B cell population in the genital tract consistent with histopathology seen in mouse and human Chlamydia infections, and discovery of a novel CD4 T cell subset based on production of IFN-ɣ and IL-13. We discuss these results in the context of Trm and previously published data showing that in humans a peripheral blood mononuclear IL-13 response to elementary bodies (EB) predicts resistance to future infection.
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Project description:The female genital tract (FGT) represents a complex and dynamic environment with specialized immune mechanisms uniquely designed to maintain a delicate balance between protection against invading pathogens and accommodating the unique physiological changes associated with reproductive function. Dendritic cells (DCs) are critical in shaping mucosal immunity against pathogens and maintaining tissue homeostasis. The unique ability of DCs to recognize invading pathogens through pattern recognition receptors (PRRs), and prime naive T cell function, make DCs ideal targets for vaccination and therapeutic strategies against cancers and infections. DC subsets and mononuclear phagocyte populations at human mucosal surfaces remain poorly defined. Local characterization of these populations is important, since DCs and mononuclear phagocyte populations are highly specialized depending on the tissue of residence.
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Project description:Chlamydia trachomatis is an obligate intracellular Gram-negative bacterium that frequently causes an asymptomatic genital tract infection, gradually cleared by host immunity Transcriptome profiles were made of endometrial tissue from women with or without genital tract C. trachomatis infection, to characterize host responses to infection. Profiles showed that infection polarized host defense toward Type 2 immune responses. Responses included fibrin deposition, enhanced wound repair, and tissue remodeling. Trans-cervical endometrial biopsy specimens were collected from 10 women with no identified upper or lower genital tract infection and 12 women with C. trachomatis endometrial infection.
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Project description:In this study, we used a bead-based affinity proteomics method to examine genital proteins in women living in HIV-serodiscordant relationships. Proteins identified using the affinity set-up were validated by a label free tandem mass spectrometry based method in a parallel cohort with concordant results.
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Project description:Chlamydia trachomatis is an obligate intracellular Gram-negative bacterium that frequently causes an asymptomatic genital tract infection, gradually cleared by host immunity Transcriptome profiles were made of endometrial tissue from women with or without genital tract C. trachomatis infection, to characterize host responses to infection. Profiles showed that infection polarized host defense toward Type 2 immune responses. Responses included fibrin deposition, enhanced wound repair, and tissue remodeling.
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Project description:The seminal plasma (SP) modulates the female reproductive immune environment after mating and microRNAs (miRNAs) could participate in the process. Considering the boar ejaculate is built by fractions differing in SP-composition; this study evaluated whether exposure of mucosal explants of the sow internal genital tract (uterus, utero-tubal junction and isthmus) to different SP-fractions changed the profile of explant-secreted miRNAs. Mucosal explants retrieved from oestrus sows (n=3) were in vitro exposed to: Medium 199 (M199, Control) or M199 supplemented (1:40 v/v) with SP from the sperm-rich fraction (SRF), the post-SRF or the entire recomposed ejaculate, for 16 h. After, the explants were cultured in M199 for 24 h to finally collect the media for miRNA analyses using GeneChip miRNA 4.0 Array (Affymetrix). Fifteen differentially expressed (False‐Discovery-Rate < 0.05 and Fold-change ≥ 2) miRNAs (11 down- vs 4 up-regulated) were identified (the most in the media of uterine explants incubated with SP from post-SRF). Bioinformatics analysis identified that predicted target genes of dysregulated miRNAs, mainly miR-34b, miR-205, miR-4776-3p and miR-574-5p, were involved in functions and pathways related to immune response. In conclusion, SP is able to elicit changes in the miRNAs profile secreted by female genital tract, ultimately depending SP-composition.
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