Innate and Adaptive Immune Responses Induced by A. Fumigatus Conidia and Hyphae

Abstract Purpose Previous research indicated hyphae of A. fumigatus rather than conidia could successfully build pulmonary aspergillosis model in immunocompetent mice. In this study, we compared the immune responses induced by hyphae and conidia, making a preliminary explanation for the phenomenon.Methods Macrophages and PBMCs were respectively stimulated by A. fumigatus hyphae and conidia and immunological changes were measured in vitro. Male C57BL/6 mice were challenged with conidia and hyphae through intratracheal inoculation. Dynamic conditions of mice were recorded and their immune responses were measured by RNA-seq.Results The results confirmed that hyphae could induce more intensive inflammation than conidia. However, macrophages revealed a higher production of ROS as well as M1 polarization in response to conidia stimuli. In addition, conidia could promote Th1 cell differentiation, while hyphae could increase the CD4/CD8 ratio. RNA-seq validated that multiple immunologically relevant pathways were much more strongly activated by hyphae, which also promoted Th2 cell differentiation and suppressed Th1 cell differentiation. Both hyphae and conidia could activate Th17 cell differentiation.Conclusion Conidia and hyphae induced different immune responses and the immune responses against conidia played a better protective role.