An altered cross-talk between gut microbiota, the intestinal epithelium, and the immune system may lead to bacterial translocation, Toll-like receptor (TLR)-activation, and IFN-induction, and this appears to contribute to the CD4 T cell exhaustion and functional impairment observed in some CVID patients [40, 41]. This evidence concerns the gene IFNA1 and common variable immunodeficiency.