Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques.
Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit(+)IL-7Rα(+) (CD117(+)CD127(+)) cells. These ILC3 cells highly expressed CD90 (∼ 63%) and aryl hydrocarbon receptor and produced IL-17 (∼ 63%), IL-22 (∼ 36%), and TNF-α (∼ 72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4(+) T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P < 0.001). Notably, ILC3 could be induced to undergo apoptosis by microbial products through the TLR2 (lipoteichoic acid) and/or TLR4 (LPS) pathway. These findings indicated that persistent microbial translocation may result in loss of ILC3 in lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues.
Division of Comparative Pathology, Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, USA hxu@tulane.edu rveazey@tulane.edu.
Huanbin
H
Xu
Division of Comparative Pathology, Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, USA.
Xiaolei
X
Wang
Division of Comparative Pathology, Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, USA.
Andrew A
AA
Lackner
Division of Comparative Pathology, Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, USA hxu@tulane.edu rveazey@tulane.edu.
Ronald S
RS
Veazey
D000818:Animals; D007113:Immunity, Innate; D008212:Lymphocyte Depletion; D008221:Lymphoid Tissue / Q000378:metabolism*; D008251:Macaca; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000502:physiology*
D051193:Toll-Like Receptors
GALT; HIV; ILC; SIV