The intricate cross-talk of the microbiome in Resistance and Tolerance to pathogens
The diverse microbial population characterizing the human host represents the result of different complex scenarios impacting the human microbiome assembly. The variety of the microbial species involved plays an important role on the human health by affecting the tissue differentiation, the modulation of the immune system as well as the general response against infectious pathogens, which has been recently revised and divided into two different strategies named Resistance and Tolerance. Resistance being the strategy where the host protects himself by reducing the pathogen load whereby the Tolerance being the opposite strategy, which consists in tolerating the pathogen to avoid tissue damage due to the occurrence of subsequent inflammatory pathologies. The host microbiome seems to play a crucial role in determining which strategy the host will exploit to avoid infection. We recently found that highly adaptive lactobacilli, switching from sugar to Tryptophan (Trp) as an energy source are expanded and produce an aryl hydrocarbon receptor (AhR) ligand—indole-3-aldehyde—that contributes to AhR-dependent IL-22 transcription, which then trigger the release of antimicrobial peptides by the gut epithelium. Importantly, innate lymphocytes IL-22 producers were already described as a typical innate Resistance strategy to protect the host from intragastrical Candida albicans infections in mice. Thus, the resulting IL-22-dependent balanced mucosal response allows for survival of mixed microbial communities yet provides colonization resistance to the fungus Candida albicans. Therefore, the microbiota-AhR axis might represent an important strategy pursued by co-evolutive commensalism for fine-tuning host mucosal reactivity contingent on Trp catabolism.