title: Mannose-binding lectin regulates host resistance and pathology during experimental infection with Trypanosoma cruzi.
abstract: 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.
authors.affiliation: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. antonio.rothfuchs@ki.se
authors.forename: Antonio Gigliotti
authors.initials: AG
authors.lastname: Rothfuchs
authors.forename: Ester
authors.initials: E
authors.lastname: Roffê
authors.forename: Amanda
authors.initials: A
authors.lastname: Gibson
authors.forename: Allen W
authors.initials: AW
authors.lastname: Cheever
authors.forename: R Alan B
authors.initials: RA
authors.lastname: Ezekowitz
authors.forename: Kazue
authors.initials: K
authors.lastname: Takahashi
authors.forename: Mario
authors.initials: M
authors.lastname: Steindel
authors.forename: Alan
authors.initials: A
authors.lastname: Sher
authors.forename: André
authors.initials: A
authors.lastname: Báfica
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000097:blood / Q000469:parasitology / Q000473:pathology; D014355:Chagas Disease / Q000097:blood / Q000469:parasitology* / Q000473:pathology*; D060467:Disease Resistance / Q000276:immunology*; D005355:Fibrosis; D006790:Host-Parasite Interactions / Q000276:immunology*; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D037601:Mannose-Binding Lectin / Q000097:blood / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000473:pathology; D059208:Parasite Load; D014349:Trypanosoma cruzi / Q000502:physiology*
chemical_list: D053762:Interleukin-12 Subunit p40; D037601:Mannose-Binding Lectin