Paracoccidioides brasiliensis activates mesenchymal stem cells through TLR2, TLR4, and Dectin-1

Numerous researchers have described the potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) for the treatment of various infectious and inflammatory diseases. However, contrary to what has been reported, the transplantation of BM-MSCs in a mouse model of Paracoccidioides brasiliensis-induced pulmonary fibrosis exacerbated the inflammatory process and fibrosis, worsening the course of the infection. The aim of this work was to determine whether P. brasiliensis exerts an immunomodulatory effect on BM-MSCs. The results indicate that P. brasiliensis can activate BM-MSCs through a mechanism dependent on TLR2, TLR4 and Dectin-1. In addition, it was found that these fungal cells can adhere and internalize within BM-MSCs. Nonetheless, this process did not affect the survival of the fungus and on the contrary, triggered the expression of inflammatory mediators such as IL-6, IL-17, TNF-alpha, and TGF-beta. The present findings correlate with the loss of a fungicidal effect and poor control of the fungus, evidenced by the count of the colony-forming units. Previously reported in vivo results are thus confirmed, showing that P. brasiliensis induces an inflammatory profile in BM-MSCs when producing pro-inflammatory molecules that amplify such response.