Histoplasma capsulatum modulates the immune response, affects proliferation and differentiation, and induces apoptosis of mesenchymal stromal cells.

ABSTRACT

Mesenchymal stromal cells (MSC) have been widely used not only for tissue regeneration but also for the treatment of various diseases; however, it has been shown that infection of MSCs by different pathogens can attenuate their intrinsic immunomodulatory properties, affecting the proliferation and differentiation of these cells. Currently, the mechanisms by which MSCs respond to pathogen invasion are poorly understood. Therefore, the objective of the present study was to determine if the infection of bone marrow-derived MSCs, with yeasts of the pathogenic fungus Histoplasma capsulatum affects the activation, differentiation and/or proliferation of the MSCs. The results indicate that MSCs have the ability to phagocytose H. capsulatum yeasts but do not exert a notable antifungal effect. On the contrary, the infection of the MSCs with this fungal pathogen not only modulates the expression of inflammatory mediators by a mechanism dependent on TLR2, TLR4 and Dectin-1 but also affects the viability and differentiation capacity of the MSCs. These findings suggest that infection of MSCs by H. capsulatum could not only affect haematopoiesis but also modulate the immune response in the infected host and, furthermore, these MSCs could provide a niche for the fungus, allowing it to persist and evade the immune response of the host.