title: Ficolin-2 defends against virulent Mycobacteria tuberculosis infection in vivo, and its insufficiency is associated with infection in humans.
abstract: Human ficolin-2 (ficolin-2/P35) is a lectin complement pathway activator that is present in normal human plasma and is associated with infectious diseases; however, little is known regarding the roles and mechanisms of ficolin-2 during Mycobacterium tuberculosis (Mtb) infection. Here, we describe our novel findings that the ficolin-2 serum levels of 107 pulmonary tuberculosis (TB) patients were much lower compared with 107 healthy controls. In vitro analysis showed that ficolin-2 bound to the virulent Mtb H37Rv strain much more strongly than to the non-virulent M. bovis BCG and M. smegmatis. Ficolin-2 bound to the surface glycolipid portion of H37Rv and blocked H37Rv infection in human lung A549 cells. Opsonophagocytosis was also promoted by ficolin-2. Importantly, we found that administration of exogenous ficolin-2 had a remarkable protective effect against virulent Mtb H37Rv infection in both C57BL/6J and BALB/c mice. Ficolin-A (a ficolin-2-like molecule in mouse) knockout mice exhibited increased susceptibility to H37Rv infection. We further demonstrated that ficolin-2 could defend against virulent Mtb H37Rv infection at least partially by activating JNK phosphorylation and stimulating the secretion of interferon (IFN)-γ, interleukin (IL)-17, IL-6, tumor necrosis factor (TNF)-α, and nitric oxide (NO) production by macrophages. Our data provide a new immunotherapeutic strategy against TB based on the innate immune molecule ficolin-2 and indicate that ficolin-2 insufficiency is associated with higher susceptibility to infection in humans.
authors.affiliation: State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Wuhan, P. R. China.
authors.forename: Fengling
authors.initials: F
authors.lastname: Luo
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Sun
authors.forename: Yubin
authors.initials: Y
authors.lastname: Wang
authors.forename: Qilong
authors.initials: Q
authors.lastname: Wang
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Wu
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.forename: Chao
authors.initials: C
authors.lastname: Fang
authors.forename: Xiao-Lian
authors.initials: XL
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D000818:Animals; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D006017:Glycolipids / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D037102:Lectins / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity*; D009569:Nitric Oxide / Q000096:biosynthesis; D010766:Phosphorylation; D011485:Protein Binding; D014376:Tuberculosis / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000401:mortality; D014774:Virulence; D055815:Young Adult; D000097604:Ficolins
chemical_list: D016207:Cytokines; D006017:Glycolipids; D018836:Inflammation Mediators; D048031:JNK Mitogen-Activated Protein Kinases; D037102:Lectins; D008563:Membrane Lipids; D009569:Nitric Oxide; D000097604:Ficolins
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