NK cell spatial dynamics and IgA responses in gut-associated lymphoid tissues during SIV infections

Abstract

HIV infection induces tissue damage including lymph node (LN) fibrosis and intestinal epithelial barrier disruption leading to bacterial translocation and systemic inflammation. Natural hosts of SIV, such as African Green Monkeys (AGM), do not display tissue damage despite high viral load in blood and intestinal mucosa. AGM mount a NK cell-mediated control of SIVagm replication in peripheral LN. We analyzed if NK cells also control SIVagm in mesenteric (mes) LN and if this has an impact on gut humoral responses and the production of IgA known for their anti-inflammatory role in the gut. We show that CXCR5 + NK cell frequencies increase in mesLN upon SIVagm infection and that NK cells migrate into and control viral replication in B cell follicles (BCF) of mesLN. The proportion of IgA+ memory B cells were increased in mesLN during SIVagm infection in contrast to SIVmac infection. Total IgA levels in gut remained normal during SIVagm infection, while strongly decreased in intestine of chronically SIVmac-infected macaques. Our data suggest an indirect impact of NK cell-mediated viral control in mesLN during SIVagm infection on preserved BCF function and IgA production in intestinal tissues.

Early antiretroviral therapy favors post-treatment SIV control associated with expansion of enhanced memory CD8+ T cells. pVISCONTI study

“…Early ART initiation has been shown to preserve the gut epithelial barrier and associated lymphoid tissues, decreasing bacterial translocation and inflammation, and favoring the persistence of IgA-secreting cells 58 . In the natural host, where the epithelial barrier is preserved as well, higher IgA levels than in macaques have been reported 43 . Despite that higher IgA/IgG ratios in W4-treated animals observed at ART initiation and at the time of ART interruption were likely associated with the higher levels of anti-gp140 IgGs in the W24-treated animals at these time points, the higher ratios still present at day 28 post-ATI could originate from preserved gut-derived IgA responses in W4-treated macaques, but this deserves further investigation.…”

“…SIVmac 251 g140 foldon-type glycoproteins were produced by transient transfection of FreeStyle™ 293-F cells, and purified by affinity chromatography using Ni Sepharose® Excel beads (GE Healthcare) as previously described 43 . High-binding 96-well ELISA plates (Costar, Corning) were coated overnight with 250 ng/well of purified recombinant SIV gp140 proteins After washings with 0.05% Tween 20-PBS (washing buffer), plates were blocked 2 h with 2% BSA, 1 mM EDTA, 0.05% Tween 20-PBS (blocking buffer), washed, and incubated with serially diluted NHP sera in duplicate at 1:250 or 1:50 following by 7 consecutive 1:4 or 1:3 dilutions in PBS for IgG or IgA detection, respectively.…”

Early antiretroviral therapy favors post-treatment SIV control associated with the expansion of enhanced memory CD8+ T-cells

“…SIVmac 251 g140-foldon-type glycoproteins were produced by transient transfection of FreeStyle™ 293-F cells and purified by affinity chromatography using Ni Sepharose® Excel beads (GE Healthcare) 74 . Highbinding 96-well ELISA plates (Costar, Corning) were coated overnight with 250 ng/well of purified recombinant SIV gp140 protein.…”

Making a Monkey out of Human Immunodeficiency Virus/Simian Immunodeficiency Virus Pathogenesis: Immune Cell Depletion Experiments as a Tool to Understand the Immune Correlates of Protection and Pathogenicity in HIV Infection

“…The loss of IgA in plasma correlates with the loss of IgA in intestine during HIV/SIV infection. Hypergammaglobulinemia is associated with chronic SIV pathogenic infection but not with nonprogression in natural hosts [ 94 , 95 , 96 , 97 ]. The V2 loop is included in the CCR5 receptor-binding site and contains the α4β7 mucosal homing integrin-binding site [ 98 , 99 ].…”