Bat-mouse bone marrow chimera: a novel animal model for dissecting the uniqueness of the bat immune system

Yong, Kylie Su Mei; Ng, Justin Han Jia; Her, Zhisheng; Hey, Ying Ying; Tan, Sue Yee; Tan, Wilson Wei Sheng; Irac, Sergio Erdal; Liu, Min; Chan, Xue Ying; Gunawan, Merry; Foo, Randy Jee Hiang; Low, Dolyce Hong Wen; Mendenhall, Ian Hewitt; Chionh, Yok Teng; Dutertre, Charles-Antoine; Chen, Qingfeng; Wang, Lin-Fa

In order to uncover if bat-mice had immune-mediated tissue damage in the absence of observable clinical signs, histological analysis was applied to assess pathological changes in different organs from bat-mice. In most acute symptoms of graft rejection, the first organs affected with tissue damage are the liver, skin and intestinal tract 34, 50 . Transplantation of C57BL/6 splenocytes and human peripheral mononuclear cells (PBMCs) separately into NSG mice were used as a positive control as they have been known to induce graft rejection in recipients with different genetic backgrounds 35, 38, 43, 44 . Two to four weeks post-transplantation, recipients of 1 × 10 6 C57BL/6 splenocytes or 1 × 10 6 human PBMCs displayed symptoms of runt disease, a condition that features small and weaken mice, characteristic of graft rejection 51 . Organs were harvested from these mice and compared to bat-mice via histological and pathological analysis. Massive cell infiltration and damages were observed in various organs from mice that received C57BL/6 splenocytes or human PBMCs, while there was no significant difference between NSG mice and bat-mice, both of which were without any evident signs of clinical abnormalities (Fig. 2d) . These results confirmed that mature bat immune cells did not induce rejection in NSG mice.