Compartment specific changes of innate lymphoid cells within the intestinal mucosa of HIV-1 infected individuals
Background: HIV infection occurs predominantly in the mucosal surfaces of the gastrointestinal tract and is associated with compromised intestinal barrier integrity and dysbiosis that is not reversed by current antiretroviral therapy (ART). Innate lymphoid cells (ILCs) orchestrate mucosal barrier de...
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| Published in: | Journal of the International AIDS Society Vol. 24; no. S1; p. 14 |
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| Main Authors: | , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
International AIDS Society
01-01-2021
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Background: HIV infection occurs predominantly in the mucosal surfaces of the gastrointestinal tract and is associated with compromised intestinal barrier integrity and dysbiosis that is not reversed by current antiretroviral therapy (ART). Innate lymphoid cells (ILCs) orchestrate mucosal barrier defences and are involved in the regulation of tissue homeostasis. However, the impact of HIV-1 infection on ILCs in the human intestinal mucosa and gut draining lymphoid tissue is unknown. Methods: Here, we present a large cohort of patients from a gastrointestinal clinic in KwaZulu-Natal, South Africa recruited within extremely high HIV endemic areas. Human gut draining lymph nodes and intestinal biopsies were collected during surgical procedures. Phenotypic characterization of ILCs was done using flow cytometry and immunohistochemistry. Moreover, we employed single-cell transcriptomics of pre-sorted ILCs to examine the gene expression profile and ex vivo response to HIV infection. Results: Total ILC levels in the gut of HIV uninfected individuals were comparable. However, we found ILC subtype-specific and regional changes between the small and large intestine. Intraepithelial ILC1 (p < 0.0001) and NK cells (p < 0.0001) were significantly enriched in the duodenum compared to the colon, whereas ILC3s were significantly expanded in the colon compared to the duodenum (p < 0.0001) in HIV uninfected individuals. In HIV infected participants, we observed expansion of duodenal ILC3s (p = 0.03) that was not found within the colon compared to HIV uninfected participants. The gut compartment-specific difference in ILC3 levels was independent of CD4 T-cell depletion observed in both compartments (p < 0.0001). We found modest changes in ILC3 levels within gut lymph nodes in HIV infected and uninfected individuals. Single-cell RNAseq of presorted ILCs from lymph nodes reveals tissue-specific transcriptional profiles between NK, ILC1 and ILC3 subsets with pending analysis of their response to HIV infection ex vivo. Conclusions: Compartment-specific differences in ILC subsets suggest distinct roles for these cells throughout the small and large intestine. Strikingly, ILC subset change in response to HIV infection within the small intestine with enriched ILC3s in HIV infected duodenal biopsies, irrespective of CD4 T cell depletion, suggests that ILC3s may play important roles in intestinal epithelial homeostasis that should be explored further for therapeutic potentials during chronic HIV-1 infection. |
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| ISSN: | 1758-2652 1758-2652 |
| DOI: | 10.1002/jia2.25659 |