Differential infection of mononuclear phagocytes by Francisella tularensis: role of the macrophage mannose receptor

Journal of Leukocyte Biology

Lee-Ann H. Allen¹  Grant S. Schulert² 

[1] Inflammation Program and Departments of Microbiology and Internal Medicine, University of Iowa and the VA Medical Center, Iowa City Inflammation Program and Departments of Inflammation Program and Departments of Microbiology and Internal Medicine, University of Iowa and the VA Medical Center, Iowa City Microbiology and Inflammation Program and Departments of Microbiology and Internal Medicine, University of Iowa and the VA Medical Center, Iowa City Internal Medicine, University of Iowa and the VA Medical Center, Iowa City Inflammation Program and Departments of Microbiology and Internal Medicine, University of Iowa and the VA Medical Center, Iowa City;Inflammation Program and Departments of Microbiology and Inflammation Program and Departments of Inflammation Program and Departments of Microbiology and Microbiology and Inflammation Program and Departments of Microbiology and

关键词: phagocytosis;    complement;    live-vaccine strain;    MDM;    tularemia;    lectinophagocytosis;   

DOI  :  10.1189/jlb.0306219

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Francisella tularensis (Ft) is a Gram-negative bacterium and the causative agent of tularemia. It is well established that this organism replicates inside macrophages, but we are only beginning to understand this interface at the molecular level. Herein, we compared directly the ability of Ft subspecies holarctica live-vaccine strain to infect freshly isolated human peripheral blood monocytes, monocyte-derived macrophages (MDM), and cells of the murine macrophage cell line J774A.1 (J774). We now show that unopsonized bacteria infected human MDM fivefold more efficiently than monocytes or J774 cells in standard media. Moreover, enhanced infection of MDM was mediated, in part, by the macrophage mannose receptor (MR). Forming Ft phagosomes accumulated MR, and infection was inhibited by MR-blocking antibody or soluble mannan but not by the dectin-1 ligand laminarin. Up-regulation of MR in MDM (by exposure to interleukin-4) increased Ft phagocytosis, as did expression of MR in J774 cells. Conversely, opsonized Ft were ingested readily by monocytes and MDM. Medium supplementation with 2.5% fresh autologous serum was sufficient to confer opsonophagocytosis and CD11b accumulated in the membrane at sites of Ft engulfment. Infection of monocytes by opsonized Ft was nearly ablated by complement receptor 3 (CR3) blockade. Conversely, MDM used MR and CD11b/CD18 to ingest opsonized organisms. Altogether, our data demonstrate differential infection of mononuclear phagocytes by Ft and define distinct roles for MR and CR3 in phagocytosis.

【 授权许可】

Unknown