Mannose-Binding Lectin Regulates Host Resistance and Pathology during Experimental Infection with Trypanosoma cruzi

PLoS One

Kazue Takahashi¹  André Báfica²  Ester Roffê³  Antonio Gigliotti Rothfuchs⁴  Allen W. Cheever⁴  R. Alan B. Ezekowitz⁴  Alan Sher⁵  Mario Steindel⁵  Amanda Gibson⁶ 

[1] Biomedical Research Institute, Rockville, Maryland, United States of America;Department of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil;Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden;Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America;Laboratory of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America;Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America

关键词: Trypanosoma cruzi;    Parasitic diseases;    Chagas disease;    Heart;    Parasite replication;    Protozoan infections;    Trypomastigotes;    Polymerase chain reaction;   

DOI  :  10.1371/journal.pone.0047835

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Mannose-binding lectin (MBL) is a humoral pattern-recognition molecule important for host defense. Although recent genetic studies suggest an involvement of MBL/MASP2-associated pathways in Chagas’ disease, it is currently unknown whether MBL plays a role in host resistance to the intracellular protozoan Trypanosoma cruzi, the causative agent of Chagas’ disease. In this study we employed MBL−/− mice to assess the role of MBL in resistance to experimental infection with T. cruzi. T. cruzi infection enhanced tissue expression of MBL both at the mRNA and protein level. Similarly, symptomatic acute Chagas’ disease patients displayed increased serum concentrations of MBL compared to patients with indeterminate, asymptomatic forms of the disease. Furthermore, increased parasite loads in the blood and/or tissue were observed in MBL−/− mice compared to WT controls. This was associated with reduced systemic levels of IL-12/23p40 in MBL−/− mice. Importantly, MBL−/− mice infected with a cardiotropic strain of T. cruzi displayed increased myocarditis and cardiac fibrosis compared to WT controls. The latter was accompanied by elevated hydroxyproline content and mRNA levels of collagen-1 and -6 in the heart. These observations point to a previously unappreciated role for MBL in regulating host resistance and cardiac inflammation during infection with a major human pathogen.

【 授权许可】

CC BY