Invariant organic killer T (iNKT) cells are innate-like T cells that

Invariant organic killer T (iNKT) cells are innate-like T cells that respond to lipid antigens presented by Compact disc1n. iNKT cell function and frequency. We discovered positive organizations between the variety of many types and iNKT cell regularity and their capability to generate IL-4 in the GALT but not really in the bloodstream. General, our outcomes are constant with the speculation that GALT iNKT cells, influenced by certain bacterial species, may play a key role in regulating immune activation in HIV-1 infection. Introduction HIV-1 infection leads to the development of chronic inflammation that persists even in antiretroviral (ART)-treated individuals with undetectable viral loads1,2. This inflammation is associated with non-HIV comorbidities, including cardiovascular disease, neurologic disorders, cancers, and an overall increased mortality. It has become apparent that immune activation is a better predictor of HIV-1 disease progression than either peripheral blood CD4+ T-cell count or viral load3, highlighting the importance of chronic immune activation. However, buy 158013-43-5 distinct pathways of immune activation (innate vs. adaptive) appear to have differential prognostic capacity, depending on the cohorts4. Importantly, while ART significantly diminishes immune activation (particularly if initiated early after infection5), levels do not normalize to those of uninfected individuals. Invariant natural killer T (iNKT) cells are innate-like T cells that respond to lipid antigens presented on CD1d, an MHC class I-like molecule expressed on antigen presenting cells (APCs)6. iNKT cells are characterized by their expression of the semi-invariant T cell receptor chain V24-J18 preferentially paired to a V11 chain. Upon stimulation, iNKT cells are capable of rapid production of a vast array of cytokines and chemokines and are instrumental in orchestrating innate and adaptive immune response7. iNKT cells can recruit and modulate other immune cells, including natural killer (NK) cells, dendritic cells (DC), and conventional CD4+ and CD8+ T cells8. Depending on the type of specific interactions between iNKT cells and DCs, the cytokines secreted by activated iNKT cells may either activate or suppress adaptive immune responses. Mouse studies have shown that the symbiotic microbiota can impact the maturation and function of iNKT cells in the mucosa9,10. A sphingolipid produced by the human commensal genus (Benjamini-Hochberg Q value < 0.15, Supplementary file), a genus that has been shown to be increased in abundance in HIV-infected subject gut microbiomes and associated with elevated mucosal immune activation31. Given that expresses a glycolipid that can activate human buy 158013-43-5 iNKT cells11, we investigated whether the abundance of (OTUs) within the genus was associated with frequencies of iNKT cells in both peripheral blood and GALT within ART-treated HIV-infected subjects, all study subjects combined, and uninfected subjects only (Figure 5B and C, Supplementary file). Fewer OTUs reached P<0.10 for comparisons to peripheral blood as opposed to GALT iNKT frequencies, and no trends were consistent across all subject groupings for comparisons to peripheral blood. However, when comparing OTU abundances to GALT iNKT frequencies, consistent positive associations were found between several OTUs and iNKT frequencies across subject groups. Finally, we looked for associations between OTUs and the capacity of GALT iNKT cells to produce IL-4 (Figure 5D, Supplementary file), though these observations exhibited Benjamini-Hochberg false Rabbit Polyclonal to RAB5C discovery rate Q values > 0.70. These results suggest that loss of the genus in HIV-infected individuals could influence both the frequency and function of iNKT cells in the gut. Figure 5 Change in microbiota in HIV-infected individuals and associations with iNKT frequency and function Discussion Several studies have examined the frequency and function of peripheral blood iNKT cells in HIV-1 infection but limited information is available for the GALT, an important target in HIV-1 pathogenesis. We found that iNKT cells were depleted in the buy 158013-43-5 blood but not in the GALT of HIV-infected subjects and that GALT iNKT cells consisted of an increased proportion of the CD4+ subset. This is in contrast to a previous study that reported that CD4+ iNKT cells are lost in the gut of HIV-1-infected individuals32. The discrepancy between our results and buy 158013-43-5 those of Ibarrondo who have shown that.

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