Presence of Inflammatory Group I and III Innate Lymphoid Cells in the Colon of Simian Immunodeficiency Virus-Infected Rhesus Macaques
Presence of Inflammatory Group I and III Innate Lymphoid Cells in the Colon of Simian Immunodeficiency Virus-Infected Rhesus Macaques
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DOI：
10.1128/jvi.01914-19
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发表时间：
2020-05-01
影响因子：
5.4
通讯作者：
Barker, Edward
中科院分区：
文献类型：
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作者：
Cogswell, Andrew;Ferguson, Natasha;Barker, Edward
Chronic, low-grade, systemic, and mucosal inflammation correlates with increased morbidity and poor clinical outcomes among patients living with human immunodeficiency virus (HIV). These long-term complications are linked to the disruption of gastrointestinal (GI) tract epithelial barrier integrity and subsequent microbial translocation. However, the mechanisms responsible for these downstream effects of infection are unknown. Here, we demonstrate that during the disruption of the GI tract and increased microbial translocation, we find inflammatory cytokines (e.g., interferon gamma [IFN-gamma] and tumor necrosis factor alpha [TNF-alpha]) produced by innate lymphoid cells (ILCs) located in the colon secondary to simian immunodeficiency virus (SIV) infection. To do this, we used viably cryopreserved colon cells from SIV-infected and uninfected rhesus macaque monkeys and determined the make-up of the ILC subpopulations and the cytokines they expressed constitutively. Our studies revealed that the interleukin-22 (IL-22)/IL-17-producing ILCS was not altered during SIV infection. However, the percentage of IFN-gamma(+) ILCs in infected colons was 5- to 10-fold higher than that in uninfected colons. ILCs from infected tissue that produced IFN-gamma also expressed TNF-alpha and IL-22. The coexpression of inflammatory cytokines with IL-22 is linked to the ability of ILCs to coexpress T-bet and ROR gamma T/Ahr. The expression of IFN-gamma/TNF-alpha by ILCs and NK cells combined likely triggers a pathway that contributes to chronic mucosal inflammation, GI barrier breakdown, and microbial translocation within the context of SIV/HIV infection.IMPORTANCE There is a slow yet significant uptick in systemic inflammation secondary to HIV infection that has long-term consequences for the infected host. The systemic inflammation most likely occurs as a consequence of the disruption of the gut epithelial barrier, leading to the translocation of gut microbial products. This disruption may result from mucosal inflammation. Here, we show in an animal model of HIV that chronic SIV-infected gut contains innate lymphoid cells producing inflammatory cytokines.
