title: Mycobacterium avium infection in CD14-deficient mice fails to substantiate a significant role for CD14 in antimycobacterial protection or granulomatous inflammation.
abstract: CD14 is a pattern-recognition receptor implicated in the inflammatory response to microbial components such as lipopolysaccharide, peptidoglycan and lipoarabinomannan. In this work, we made use of CD14-deficient (CD14-/-) mice to evaluate the relative importance of CD14 in response to infection with viable, intact cells of Mycobacterium avium in vitro and in vivo. Following co-incubation of either bone marrow-derived macrophages (Mphi) or thioglycollate-elicited peritoneal Mphi from CD14-/- mice with viable M. avium, tumour necrosis factor (TNF) production was significantly reduced and delayed compared to TNF secretion by infected CD14+/+ Mphi. However, following intravenous infection with a M. avium strain of either high virulence (TMC724) or intermediate virulence (SE01), there was no difference in the bacterial loads of lungs, livers or spleens at 3, 5 and 8 weeks postinfection in CD14-/- mice when compared with syngeneic CD14+/+ mice. At these time-points, TNF and interferon-gamma (IFN-gamma) mRNA expression in the liver was similar in infected CD14+/+ and CD14-/- mice, and granuloma formation and expression of inducible nitric oxide synthase within granuloma Mphi was the same in both mouse groups. In conclusion, although the absence of CD14 results in significantly reduced and delayed TNF production in response to stimulation with M. avium in vitro, there is no evidence that CD14 plays a significant role in either the antibacterial defence or the chronic granulomatous reaction to M. avium infection in vivo.
authors.affiliation: Division of Molecular Infection Biology, Research Center Borstel, Borstel, Germany. sehlers@fz-borstel.de
authors.forename: S
authors.initials: S
authors.lastname: Ehlers
authors.forename: N
authors.initials: N
authors.lastname: Reiling
authors.forename: S
authors.initials: S
authors.lastname: Gangloff
authors.forename: A
authors.initials: A
authors.lastname: Woltmann
authors.forename: S
authors.initials: S
authors.lastname: Goyert
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D018929:Cell Culture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006099:Granuloma / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009164:Mycobacterium Infections / Q000276:immunology*; D009162:Mycobacterium avium; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger