CD14 contributes to pulmonary inflammation and mortality during murine tuberculosis.
Toll-like receptors play an essential role in the innate recognition of micro-organisms by the host. CD14 is one of the extracellular adaptor proteins required for recognition of Gram-negative bacteria and possibly also Mycobacterium tuberculosis. Therefore, we intranasally infected wild-type (WT) and CD14 knock-out (KO) mice with virulent M. tuberculosis H37Rv. We found no differences in bacterial load in the main target organ lung up to 32 weeks after infection. From 20 weeks onward 57% of WT mice succumbed, whereas all CD14 KO mice survived. The improved outcome of CD14 KO mice was accompanied by reduced pulmonary inflammation; lung cell counts and percentage of inflamed lung tissue were reduced in CD14 WT mice. These data suggest that during chronic infection CD14 KO mice are protected from lethality caused by lung tuberculosis because of a reduction of the inflammatory response.
Wieland
Catharina W
CW
Center of Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, The Netherlands. c.wieland@amc.uva.nl
van der Windt
Gerritje J W
GJ
Wiersinga
W Joost
WJ
Florquin
Sandrine
S
van der Poll
Tom
T
D000818:Animals; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000472:pathogenicity*; D011014:Pneumonia / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D014774:Virulence
D018925:Chemokines; D016207:Cytokines; D018950:Lipopolysaccharide Receptors