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Brief Report: Inflammatory Colonic Innate Lymphoid Cells Are Increased During Untreated HIV-1 Infection and Associated With Markers of Gut Dysbiosis and Mucosal Immune Activation.
Dillon, Stephanie M. PhD *; Castleman, Moriah J. PhD *; Frank, Daniel N. PhD *,+; Austin, Gregory L. MD, MPH ++; Gianella, Sara MD [S]; Cogswell, Andrew C. BA ||; Landay, Alan L. PhD ||; Barker, Edward PhD ||; Wilson, Cara C. MD *
[Miscellaneous Article] JAIDS Journal of Acquired Immune Deficiency Syndromes. 76(4):431-437, December 1, 2017.

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Background: HIV-1 infection is associated with intestinal inflammation, changes in the enteric microbiota (dysbiosis), and intestinal epithelial cell damage. NKp44 innate lymphoid cells (ILCs) play an important role in epithelial barrier maintenance through the production of interleukin (IL)-22 but also display functional plasticity and can produce inflammatory cytokines [eg, interferon gamma (IFN[gamma])] in response to cytokine milieu and stimulatory signals. The objective of this pilot study was to enumerate frequencies of IL-22 and IFN[gamma]-expressing colonic NKp44 ILCs during untreated, chronic HIV-1 infection.

Setting: A cross-sectional study was performed to compare numbers of cytokine-expressing ILCs in colonic biopsies of untreated, chronic HIV-1 infected (n = 22), and uninfected (n = 10) study participants. Associations between cytokine ILC and previously established measures of virological, immunological, and microbiome indices were analyzed.

Methods: Multicolor flow cytometry was used to measure the absolute number of colonic CD3-NKp44 /-CD56 /- ILCs expressing IL-22 or IFN[gamma] after in vitro mitogenic stimulation.

Results: Numbers of colonic NKp44 ILCs that expressed IFN[gamma] were significantly higher in HIV-1 infected versus uninfected persons and positively correlated with relative abundances of dysbiotic bacterial species in the Xanthomonadaceae and Prevotellaceae bacterial families and with colonic myeloid dendritic cell and T-cell activation.

Conclusion: Higher numbers of inflammatory colonic ILCs during untreated chronic HIV-1 infection that associated with dysbiosis and colonic myeloid dendritic cell and T-cell activation suggest that inflammatory ILCs may contribute to gut mucosal inflammation and epithelial barrier breakdown, important features of HIV-1 mucosal pathogenesis.