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OSU researcher advancing knowledge on fungal stealth technology

The normal host immune system detects invading microbes by recognizing specific features on the surface of the microbe leading to the activation of host defense mechanisms. In order to cause disease, pathogens must subvert this detection. Researcher Chad Rappleye, a new faculty member in the Departments of Microbiology and Internal Medicine and the Center for Microbial Interface Biology together with collaborators at Washington University have discovered one way in which fungal pathogens hide from immune cells. They found that pathogenic forms of Histoplasma capsulatum cells surround themselves with a specific polysaccharide which is absent from non-pathogenic fungal cells. Rappleye and co-researchers determined that this polysaccharide acts as a mask, effectively concealing Histoplasma from the immune system thereby enabling infections to progress undetected.

Successful infection by fungal pathogens depends on subversion of host immune mechanisms that detect conserved cell wall components such as beta-glucans. A less common polysaccharide, alpha-(1,3)-glucan, is a cell wall constituent of most fungal respiratory pathogens and has been correlated with pathogenicity or linked directly to virulence. However, the precise mechanism by which alpha-(1,3)-glucan promotes fungal virulence is unknown. Here, we show that alpha-(1,3)-glucan is present in the outermost layer of the Histoplasma capsulatum yeast cell wall and contributes to pathogenesis by concealing immunostimulatory beta-glucans from detection by host phagocytic cells. Production of proinflammatory TNF-alpha by phagocytes was suppressed either by the presence of the alpha-(1,3)-glucan layer on yeast cells or by RNA interference based depletion of the host beta-glucan receptor dectin-1. Thus, we have functionally defined key molecular components influencing the initial host–pathogen interaction in histoplasmosis and have revealed an important mechanism by which H. capsulatum thwarts the host immune system. Furthermore, we propose that the degree of this evasion contributes to the difference in pathogenic potential between dimorphic fungal pathogens and opportunistic fungi.

Click here to read the PNAS article in its entirety


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