Gut inflammation and indoleamine deoxygenase inhibit IL-17 production and promote cytotoxic potential in NKp44+ mucosal NK cells during SIV infection

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

“…Indeed, both SIV-infected RM and HIV-infected persons experience a significant and preferential reduction of the IL-17-producing CD4 ϩ (Th17) and CD8 ϩ (Tc17) T-cell subsets throughout the gastrointestinal tract (81)(82)(83)(84). Similarly, the depletion of IL-17-producing innate lymphocytes in the GI tracts of SIV-infected Asian macaques has been demonstrated (85,86).…”

Plasmacytoid dendritic cells promote HIV-1–induced group 3 innate lymphoid cell depletion

“…IL-17 and IL-22 are important for protection against mucosal bacterial infections and for maintenance of the mucosal barrier by promotion of intestinal epithelial integrity (24,39,40). Multiple immune cells, including Th17 cells (44), NKp44 + NK22 cells (7,22,25), and CD3 -CD8 hi subsets (21), could produce these 2 cytokines. The loss of these cells in chronic HIV-1/SIV infection has been correlated with breakdown of intestinal mucosal integrity, resulting in microbial translocation, chronic immune activation, and disease progression (21,22,24,25,(45)(46)(47).…”

“…Multiple immune cells, including Th17 cells (44), NKp44 + NK22 cells (7,22,25), and CD3 -CD8 hi subsets (21), could produce these 2 cytokines. The loss of these cells in chronic HIV-1/SIV infection has been correlated with breakdown of intestinal mucosal integrity, resulting in microbial translocation, chronic immune activation, and disease progression (21,22,24,25,(45)(46)(47). The present study extends the notion that the numeral and functional loss of the tissue-resident ILC3s also contribute to the pathogenesis induced by persistent HIV-1 infection.…”

Natural killer (NK) and NK-like cells at mucosal epithelia: Mediators of anti-microbial defense and maintenance of tissue integrity

“…Upon infection with simian immunodeficiency virus (SIV), these gut NK-22-like cells were reduced in number and showed altered functions, resulting in a change of cytokine expression toward IFN-γ. Furthermore, these cells gained cytolytic potential, as evidenced by increased perforin expression and enhanced degranulation [48]. At present, the significance of the altered NK cell functions during SIV infection is unknown, but a loss of IL-17 and IL-22 contributes to the gut pathology seen in SIV infection [49], and NK-22 cell depletion during SIV infection may thus potentially contribute to the loss of gut integrity.…”

“…In humans, human immunodeficiency virus (HIV) is an important pathogen causing high viral burden in the gut, associated with intestinal pathology [47]. A recent study has explored whether NK-22 cells are present in non-primate intestinal tissue [48]. This study by Reeves et al identified NK cells exhibiting an NK-22 phenotype in the gut of macaques, which expressed high transcript levels of IL-22 and, in contrast to human NK-22 cells, also produced IL-17.…”