AN ESSENTIAL ROLE OF IgT IN HOST-MICROBIOAL HOMEOSTASIS
Yasuhiro Shibasaki, University of Pennsylvania
Fumio Takizawa1, Zhen Xu1, Yasuhiro Shibasaki1, Thomas Sauters3, Irene Salinas3, J. Oriol Sunyer1.
1. University of Pennsylvania, Philadelphia, PA, USA
2. Department of Aquatic Animal Medicine, Huazhong Agricultural University, Wuhan, China
3. Department of Biology, University of New Mexico, Albuquerque, NM, USA
The vast majority of fish pathogens enter their host through mucosal surfaces. We have demonstrated in rainbow trout that pathogen-specific mucosal antibody responses are mediated IgT. In addition, we have shown that IgT is the main immunoglobulin isotype coating commensal bacteria. While these IgT activities point to a pivotal role of this immunoglobulin in teleost mucosal immunity, whether IgT is required for pathogen clearance and microbiota homeostasis remains to be demonstrated. Here we studied whether IgT is required for microbiota homeostasis. To address this question, we developed an IgT+ B-cell depletion model in rainbow trout. Upon one depletion treatment, IgT+ B cells were depleted by over 95% in all tested mucosal and systemic lymphoid organs. Strikingly, these cells remained depleted for a 3-4 week period. After two weeks of the treatment, the percentage of microbiota coated by IgT was drastically reduced from ~40-50% to ~0-2%. In addition, we found a high amount of microbiota translocated into the gill tissue of IgT-depleted fish. This translocation correlated with the upregulation of key pro-inflammatory cytokines as well as with substantial alterations in gill morphology. Critically, significant changes were detected in the gill microbiome of IgT-depleted fish, thus confirming further the induction of dysbiosis in the gill as result of IgT depletion. In conclusion, we demonstrate that IgT plays a critical role in the maintenance of microbiota homeostasis in a fish mucosal surface. We anticipate this novel IgT+ B-cell depletion model will be important to understand further the role of IgT in host-microbiota interactions.