Diverse strain immune reactivity shapes fungal inflammation or tolerance

For over a century microbiology and immunology have classified microorganisms in pathogenic or non-pathogenic. This definition, clearly relevant at the level of strain and species for most bacteria, has never been probed in fungal species. Understanding the nature of fungal pathogenesis will result in developing more effective therapies for fighting invasive fungal infection. Currently, several studies attempt to address pathogenicity mechanisms using different strains as a model. This study was designed to explore the immune-based diversity of Aspergillus spp strains, and Saccharomyces cerevisiae fungal strains comparing different fungal life stages, from conidia to hyphae to spores. Our results show a wide strain-dependent variation of the immune response elicited indicating that different isolates possess diverse virulence and infectivity. Moreover, in contrast to the S. cerevisiae yeast cell-induced Th1 response, dendritic cells stimulated with yeast spores induce cellular responses shifted towards Th17 differentiation. The switch between spores and yeast is crucial for the commensalism of S. cerevisiae and depends on the use of a different receptor repertoire. We demonstrate that the differential recognition of specific mannan structures is one of the master regulator of the discrimination between harmful and harmless fungi. The in-vitro preliminary classification and characterization of fungal biodiversity in inducing immune responses led us to start the investigation on how/if the different cell mediated immunogenicity could result in differences in trained immunity properties of the tested S. cerevisiae strains. Thus, the definition of markers of inflammation or pathogenicity cannot be generalized. Understanding the role of cell wall composition in different strains and variation in the balance between tolerance and inflammation responses might lead to fully understand the boundaries between safety and pathogenicity.