| First Author | Luo F | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 9 | Pages | e73859 |
| PubMed ID | 24040095 | Mgi Jnum | J:207552 |
| Mgi Id | MGI:5559109 | Doi | 10.1371/journal.pone.0073859 |
| Citation | Luo F, et al. (2013) Ficolin-2 defends against virulent Mycobacteria tuberculosis infection in vivo, and its insufficiency is associated with infection in humans. PLoS One 8(9):e73859 |
| abstractText | 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)-gamma, interleukin (IL)-17, IL-6, tumor necrosis factor (TNF)-alpha, 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. |
