Cutting edge: Toll-like receptor (TLR)2- and TLR4-mediated pathogen recognition in resistance to airborne infection with Mycobacterium tuberculosis.
Innate resistance against Mycobacterium tuberculosis is thought to depend critically on engagement of pattern recognition receptors on macrophages. However, the relative contribution of these receptors for containing M. tuberculosis infection has remained unexplored in vivo. To address this issue, we infected mice defective in CD14, TLR2, or TLR4 with M. tuberculosis by aerosol. Following infection with 100 mycobacteria, either mutant strain was as resistant as congenic control mice. Granuloma formation, macrophage activation, and secretion of proinflammatory cytokines in response to low-dose aerosol infection were identical in mutant and control mice. However, high-dose aerosol challenge with 2000 CFU M. tuberculosis revealed TLR2-, but not TLR4-defective mice to be more susceptible than control mice. In conclusion, while TLR2 signaling contributes to innate resistance against M. tuberculosis in borderline situations, its function, and that of CD14 and TLR4, in initiating protective responses against naturally low-dose airborne infection is redundant.
Reiling
Norbert
N
Division of Molecular Infection Biology, Research Center Borstel, Borstel, Germany.
Hölscher
Christoph
C
Fehrenbach
Alexandra
A
Kröger
Svenja
S
Kirschning
Carsten J
CJ
Goyert
Sanna
S
Ehlers
Stefan
S
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D029721:Drosophila Proteins; D007113:Immunity, Innate / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*
D000336:Aerosols; D016207:Cytokines; D029721:Drosophila Proteins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors