Toll-like receptor 4 is not involved in host defense against pulmonary Legionella pneumophila infection in a mouse model.
Legionella pneumophila is a gram-negative microorganism that causes a severe pneumonia known as "legionnaires disease." Toll-like receptor 4 (TLR4) transduces the lipopolysaccharide signal and is therefore considered to play a role in host defense against gram-negative bacterial infection. To determine the role of TLR4 in L. pneumophila pneumonia, C3H/HeJ mice, which display a nonfunctional gene encoding TLR4 (TLR4), and wild-type (wt) C3H/HeN mice were intranasally inoculated with L. pneumophila serogroup 1. Infection proceeded in an identical way in TLR4 mutant and wt mice, as reflected by similar bacterial outgrowth in the lungs. In addition, the inflammatory responses to L. pneumophila infection-as assessed by histopathologic analysis, cell influx in bronchoalveolar lavage fluid, myeloperoxidase activity in lungs, and lung cytokine concentrations-were indistinguishable in TLR4 mutant and wt mice. These data suggest that, in this mouse model, TLR4 does not play a role in resistance to L. pneumophila.
Department of Infectious Diseases, Tropical Medicine, and AIDS, Academic Medical Center, University of Amsterdam, The Netherlands. k.d.lettinga@amc.uva.nl
Kamilla D
KD
Lettinga
Sandrine
S
Florquin
Peter
P
Speelman
Ruud
R
van Ketel
Tom
T
van der Poll
Annelies
A
Verbon
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D029721:Drosophila Proteins; D005260:Female; D006801:Humans; D016952:Legionella pneumophila / Q000472:pathogenicity*; D007877:Legionnaires' Disease / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000201:enzymology / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009195:Peroxidase / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D016207:Cytokines; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D009195:Peroxidase