Commensal Bacteria Education History Calibrate the Naivety and Activation Threshold of Adaptive Antiviral Immune System

Yanyan Zhang ^1* Baohua Li ² Sha Zhou ¹ Li Mou ³ Feng Zhang ⁴ Haibo Wu ¹ Hong Wei ⁵ Yuzhang Wu ² Lilin Ye ² Changjiang Liu ³ Jian Li ²

• ¹ Chongqing University, Chongqing, China
• ² Institute of Immunology, Third Military Medical University, Chongqing, China
• ³ NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing, China
• ⁴ Guizhou Medical University, Guiyang, Guizhou Province, China
• ⁵ Department of Animal Production and Animal Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei Province, China

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