Abstract
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 (IFNg)] in response to cytokine milieu and stimulatory signals. The objective of this pilot study was to enumerate frequencies of IL-22 and IFNg-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 CD32NKp446CD566 ILCs expressing IL-22 or IFNg after in vitro mitogenic stimulation. Results: Numbers of colonic NKp44+ ILCs that expressed IFNg 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.
Original language | English (US) |
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Pages (from-to) | 431-437 |
Number of pages | 7 |
Journal | Journal of Acquired Immune Deficiency Syndromes |
Volume | 76 |
Issue number | 4 |
DOIs | |
State | Published - 2017 |
Externally published | Yes |
Keywords
- Dysbiosis
- HIV-1
- Inflammation
- Innate lymphoid cells
- Microbial translocation
ASJC Scopus subject areas
- Infectious Diseases
- Pharmacology (medical)