Investigating the impact of HIV infection on ILC3s in human lymph nodes.
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Date
2022
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Abstract
People living with HIV (PLWH) develop extensive fibrosis and collagen deposition throughout their
lymphoid tissues not reversed by antiretroviral therapy (ART). Innate lymphoid cells (ILCs) play
essential roles in tissue homeostasis and repair, however, no studies exist on ILCs in lymph nodes (LNs)
during HIV infection. We hypothesized that ILCs are modulated by HIV infection and are involved in
the subsequent immune responses. We obtained fresh celiac, cystic, bile, falciform, common hepatic
and mesenteric LNs immediately after gastrointestinal surgery from patients recruited from areas in
KwaZulu-Natal, South Africa – home to the highest HIV prevalence in the world. LNs from PLWH
receiving ART exhibited extensive collagen deposition compared to uninfected controls characteristic
of HIV-infected LN pathology. Single-cell transcriptional profiling revealed activation of the dominant
ILC3 subset during HIV infection, suggesting ILC3s are directly involved in the HIV immune response.
HIV-infected LNs expressed more heterogenous ILC3 subsets, including ‘ex-ILC3s’. We found
signatures suggesting that HIV infection induces terminal differentiation of homeostatic ILC3
populations, whereby an ex-ILC3 population becomes distinct and may contribute to a type 1 immune
response. Since HIV infection leads to sustained inflammation in LNs, this terminal differentiation and
emergence of ex-ILC3s may be irreversible. Moreover, we found elevated levels of TGF production
by ILC3s during HIV infection which may suggest that these cells play a role in fibrosis formation,
directly or indirectly, through fibroblast-induced collagen deposition. Here, I performed the first singlecell
analysis of ILCs in HIV-infected LNs and identified ILC3s as potential contributors to LN fibrosis,
a major pathological consequence of HIV infection that warrants further investigation
Description
Masters Degree. University of KwaZulu-Natal, Durban.