C1q Confers Protection Against Cryptococcal Lung Infection by Alleviating Inflammation and Reducing Cryptococcal Virulence.

Abstract

To define the role of C1qa in host defense against Cryptococcus neoformans lung infection, we investigated its susceptibility to cryptococcal lung infection in mice deficient in complement factor C1qa (C1qa-/- ). We established a wild-type (WT) and C1qa-deficient murine inhalation model with C. neoformans. We compared the host survival rate, inflammatory responses, and pathogenicity of C. neoformans during the infection course between WT and C1qa-/- mice. The mortality rate of C1qa-deficient mice was significantly higher than that of wild-type mice. The increased formation of Titan cells in the lungs was associated with augmented inflammation in C1qa-deficient mice. The capacity of lung homogenate supernatant from C1qa-deficient mice to induce Titan formation in vitro was greater compared with that of wild-type mice. The C. neoformans isolated from the lungs of infected C1qa-deficient mice was more resistant to macrophage killing in vitro and caused significantly higher mortality after administration to mice compared with that isolated from WT mice. These findings reveal a novel role of C1qa in host defense against C. neoformans infection by regulating host inflammation and pathogen virulence and provide new insight into the C1q-mediated lung environment underlying the transition from yeast to Titan cell.