Commensal bacteria education history calibrates the naivety and activation threshold of adaptive antiviral immune system

Exhaustion of the immune system’s ability to adapt to novelty suggests that the changes it undergoes might be a consequence of an evolutionary unpredictable antigenic exposure over a lifetime. Thus, we raise the question of whether a naive immune system can manage new antigens better than an educated immune system. Here, by employing the naive immune system of germ-free (GF) mice without a history of microbial exposure, we compared their adaptive immune responses with those of the conventional (Conv) mice upon new viral infection. Interestingly, the naive GF immune system showed robust T-cell responses, with more potent memory T cells established for long-term protection, even in the condition of primary lower T-cell levels for naive GF mice. Furthermore, we found that the ABX-treated Conv mice showed impaired T-cell responses, compared with the untreated Conv ones. With the microbiota eliminated, the ABX mice still have a history of microbial exposure and education for their immune system. In summary, commensal bacteria education history calibrates the naivety and the activation threshold of the adaptive antiviral immune system.