Abstract
Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC) have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s) in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.
Highlights
Innate lymphoid cells (ILC) encompass a broad diversity of cell types including the nominal subtypes ILC1, ILC2, ILC3, and in some descriptions include traditional natural killer (NK) cells and lymphoid tissue inducer cells, all of which arise from a common lymphoid progenitor
This study showed that microbial translocation and resulting products like lipoteichoic acid or LPS via the TLR2/4 pathway can directly cause apoptosis in ILC3, further increasing HIV-induced disruption of gut-associated lymphoid tissues (GALT)
Innate lymphoid cell fill a unique and plastic niche of primarily tissue-resident cells that provide innate sources of typical T cell and NK cell produced cytokines, and they clearly have a role in innate defense and homeostasis, many unknowns remain
Summary
Innate lymphoid cells (ILC) encompass a broad diversity of cell types including the nominal subtypes ILC1, ILC2, ILC3, and in some descriptions include traditional natural killer (NK) cells and lymphoid tissue inducer cells, all of which arise from a common lymphoid progenitor. ILC1 and NK cells rely on the transcription factor T-bet and produce type I cytokines, such as IFN-γ and TNF-α, but notably ILC1 lack the complex cytotoxic functions inherent to NK cells. ILC in HIV Infection include mucosal-associated invariant T cells [11], which express a semi-invariant T cell receptor and defined phenotypically as CD3+Vα7.2 TCR+CD161high cells in humans [12, 13]. In addition to their cellular and functional plasticity, ILC have a wide tissue distribution and are thought to be some of the earliest responders to infections and other inflammatory stimuli, but the full mechanisms involved are still poorly understood. It is becoming increasingly clear that reduced IL-17 and IL-22 production during infection cannot be attributed solely to the loss of TH17/TH22 cells and that early depletion of ILC may contribute to this process
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