Evidence of MHC class I and II influencing viral and helminth infection via the microbiome in a non-human primate

Until recently, the study of major histocompability complex (MHC) mediated immunity has focused on the direct link between MHC variability and susceptibility to parasite infection. However, MHC genes can also influence host health indirectly through the sculpting of the bacterial community that in turn shape immune responses. We investigated the links between MHC class I and II gene variability gut microbiome diversity and micro- (adenovirus, AdV) and macro- (helminth) parasite infection probabilities in a wild population of non-human primates, mouse lemurs of Madagascar. This setup encompasses a plethora of underlying interactions between parasites, microbes and adaptive immunity in natural populations. Both MHC classes explained shifts in microbiome composition and the effect was driven by a few select microbial taxa. Among them were three taxa (Odoribacter, Campylobacter and Prevotellaceae-UCG-001) which were in turn linked to AdV and helminth infection status, evidence of the indirect effect of the MHC via the microbiome. Our study provides support for the coupled role of MHC variability and microbial flora as contributing factors of parasite infection. Author summaryThe selective pressure of the major histocompatibility complex (MHC) on microbial communities, and the potential role of this interaction in driving parasite resistance has been largely neglected. Using a natural population of the primate Microcebus griseorufus, we provide evidence of two outstanding findings: that MHCI and MHCII diversity shapes the composition of the gut microbiota; and that select taxa associated with MHC variability predicted adenovirus and helminth infection status. Our study highlights the importance of incorporating the microbiome when investigating parasite-mediated MHC selection.