22-ICRAD Call 2 Comparative host and species-specific immune responses of macrophages infected with zoonotic Leptospira interrogans

We aim in this innovative project to address the question of host- and species-specificity of leptospirosis, from an innate immunity point of view. We will test the hypothesis that host adaptation of leptospires relies on the species specificities of both bacterial components and host innate immune receptors. To the best of our knowledge this hypothesis has never been formulated. Our consortium will study, using different complementary approaches, these interactions in the context of different hosts and leptospiral serovars. It will expand the fragmented knowledge, mainly obtained from mice and humans, to bovine, pigs, hamsters, rats and horses, presenting a large array of clinical symptoms of leptospirosis. Moreover, the known data only emanates from a few emblematic Leptospira strains grown in vitro, all isolated from human patients and sometimes passaged in hamster. Here, we will expand the study to Argentinian strains retrieved from cattle. We also aim to get physiologic data, by directly studying at the mRNA expression level, or at a structural level, the bacterial components in contact of primary macrophages from relevant hosts. The quality of the consortium relies on previous achievements of the PIs, all internationally recognized experts in their field, and to our complementarity. We think that this project in line with the "One health" approach will bring novel data on the relationship of Leptospira with their hosts. We hope that it could also shed light on the diverse symptoms of leptospirosis observed in various animals. Finally, this project could set the basis of new perspectives of host-directed strategies to stimulate the innate immune system and fight leptospirosis and overcome the potent strategies of leptospires to escape the host defenses.