Paracoccidioides brasiliensis induces recruitment of alpha 3 and alpha 5 integrins into epithelial cell membrane rafts, leading to cytokine secretion

Paracoccidioides brasiliensis is one of the etiological agents of paracoccidioidomycosis, a human systemic mycosis, highly prevalent in Latin America. In the present work, we demonstrate that P. brasiliensis yeasts promote IL-6 and IL-8 secretion by the human lung epithelial cell line A549 in an integrin-dependent manner. In fact, small interfering RNA directed to alpha 3 and alpha 5 integrins decreased IL-6 and IL-8 levels in P. brasiliensis-infected A549 cell cultures. This fungus also led to an increase in the expression of alpha 3 and alpha 5 integrins in this epithelial cell line. In addition, P. brasiliensis yeasts promoted alpha 3 and alpha 5 integrins clustering into A549 cell membrane rafts. Furthermore, epithelial cell membrane raft disruption with nystatin decreased IL-6 and IL-8 levels in P. brasiliensis-A549 cell cultures. Therefore, by increasing host alpha 3 and alpha 5 integrins levels and clustering these receptors into membrane rafts, P. brasiliensis yeasts may modulate host inflammation. (C) 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. (AU)