원문정보
초록
영어
Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) remains a major global health problem. Human ficolin2 (L-ficolin/P35) is a recently identified lectin complement pathway activator present in normal plasma associated with infectious diseases, however, little is known about the roles and mechanisms of ficolin2 during M.tb infection.We describe in this study for the first time L-ficolin expression levels in tuberculosis (TB) patients. We found that serum levels of ficolin2 of 107 pulmonary TB patients were much lower compared with 107 healthy controls, and recurrence TB patients have even lower levels than onset TB patients. In vitro analysis showed that Ficolin2 bound to virulent M.tb H37Rv strain much stronger than to non-virulent M. bovis BCG and M. smegmatis. Ficolin2/ficolin A bound to the H37Rv surface glycolipid portion and blocked H37Rv infection to human lung A549 cells. We further determined that the extrogenous ficolin2 had remarkable protecting effects against virulent H37Rv strain infections in C57BL/6J mice. FicolinA (ficolin2 like molecule) knockout mice had greatly increased susceptibility to the H37Rv infection. Ficolin2 activated macrophages via phosphorylation of JNK and stimulated IFN-□, IL-17, TNF-□ and nitric oxide (NO) secretions. Ficolin2 also stimulated IFN-□ production of CD8+T cells, but not CD4+T cells. The opsono-phagocytosis was promoted by ficolin2 as well. Our data demonstrate that ficolin2 can defend against virulent M.tb H37Rv infection both in vitro and in vivo mainly via activating macrophage proinflammatory cytokines IFN-□ and NO production and opsonophagocytosis, and its insufficiency is associated with more susceptible infections in human.