Binding of laminin to Paracoccidioides brasiliensis induces a less severe pulmonary paracoccidioidomycosis caused by virulent and low-virulence isolates

Abstract

The pathogenic fungus Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis (PCM). This pulmonary mycosis, acquired by inhalation of airborne propagules, may disseminate to several internal organs and tissues, leading to severe disease. Adhesion to host cell components is the first step involved in dissemination of pathogens. Previous studies showed that laminin, the most abundant glycoprotein of the basement membrane, binds to P. brasiliensis yeast cells, enhancing their pathogenicity in the hamster testicle model. As PCM is primarily a pulmonary infection, we studied the influence of previous treatment of yeast cells with laminin on the course of the intratracheal infection of resistant and susceptible mice using high-virulence (Pb18) and low-virulence (Pb265) P. brasiliensis isolates. Laminin treatment did not alter fungal loads, delayed-type hypersensitivity reactions, levels of pulmonary cytokines and production of specific antibodies in any group of Pb18-infected mice. However, early in the infection, a less intense inflammatory reaction was detected in the lungs of the laminin-treated groups. In addition, laminin treatment of Pb265 resulted in a less severe infection as revealed by the lower fungal loads recovered from lungs. Antibody and cytokine levels, however, did not change after laminin treatment. Altogether, our results demonstrate that laminin binding to yeast cells diminishes P. brasiliensis pathogenicity. The lower inflammatory response observed with the virulent isolate and the decreased pulmonary fungal burden with the low-virulence isolate indicate an inhibitory effect of laminin treatment on P. brasiliensis infectivity and interaction with pulmonary host cells or extracellular matrix proteins.