HIV-1-induced cytokines deplete homeostatic innate lymphoid cells and expand TCF7-dependent memory NK cells
Wang, Yetao ; Lifshitz, Lawrence M. ; McCauley, Sean M. ; Vangala, Pranitha ; Kim, Kyusik ; Derr, Alan G. ; Jaiswal, Smita ; Kucukural, Alper ; McDonel, Patrick ; Greenough, Thomas C. ... show 3 more
Citations
Student Authors
Faculty Advisor
Academic Program
Document Type
Publication Date
Subject Area
Embargo Expiration Date
Link to Full Text
Abstract
Human immunodeficiency virus 1 (HIV-1) infection is associated with heightened inflammation and excess risk of cardiovascular disease, cancer and other complications. These pathologies persist despite antiretroviral therapy. In two independent cohorts, we found that innate lymphoid cells (ILCs) were depleted in the blood and gut of people with HIV-1, even with effective antiretroviral therapy. ILC depletion was associated with neutrophil infiltration of the gut lamina propria, type 1 interferon activation, increased microbial translocation and natural killer (NK) cell skewing towards an inflammatory state, with chromatin structure and phenotype typical of WNT transcription factor TCF7-dependent memory T cells. Cytokines that are elevated during acute HIV-1 infection reproduced the ILC and NK cell abnormalities ex vivo. These results show that inflammatory cytokines associated with HIV-1 infection irreversibly disrupt ILCs. This results in loss of gut epithelial integrity, microbial translocation and memory NK cells with heightened inflammatory potential, and explains the chronic inflammation in people with HIV-1.
Source
Wang Y, Lifshitz L, Gellatly K, Vinton CL, Busman-Sahay K, McCauley S, Vangala P, Kim K, Derr A, Jaiswal S, Kucukural A, McDonel P, Hunt PW, Greenough T, Houghton J, Somsouk M, Estes JD, Brenchley JM, Garber M, Deeks SG, Luban J. HIV-1-induced cytokines deplete homeostatic innate lymphoid cells and expand TCF7-dependent memory NK cells. Nat Immunol. 2020 Mar;21(3):274-286. doi: 10.1038/s41590-020-0593-9. Epub 2020 Feb 17. PMID: 32066947; PMCID: PMC7044076. Link to article on publisher's site
Year of Medical School at Time of Visit
Sponsors
Dates of Travel
DOI
Permanent Link to this Item
PubMed ID
Other Identifiers
Notes
Full author list omitted for brevity. For the full list of authors, see article.