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

Xu Zhao; Lei Shen; Jianming Zheng; Haiyan Zhu; Li Li; Hong Shi; Zhongqing Chen; Qian Li

doi:10.1093/ofid/ofad151

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

Open Forum Infect Dis. 2023 Mar 21;10(4):ofad151. doi: 10.1093/ofid/ofad151. eCollection 2023 Apr.

Authors

Xu Zhao¹, Lei Shen², Jianming Zheng², Haiyan Zhu³, Li Li⁴, Hong Shi⁵, Zhongqing Chen⁶, Qian Li²

Affiliations

¹ Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
² Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
³ Department of Biological Medicines & Shanghai Engineering Research Center of ImmunoTherapeutics, School of Pharmacy, Fudan University, Shanghai, China.
⁴ Laboratory of Mycology, Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
⁵ Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
⁶ Department of Pathology, Huashan Hospital, Fudan University, Shanghai, China.

Abstract

Background: 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^-/- ).

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: C1q; Cryptococcus neoformans; Titan cells; inflammatory response.