Toll-like receptors 2 and 4 do not contribute to clearance of Chlamydophila pneumoniae in mice, but are necessary for the release of monokines.
Activation of immune cells by Chlamydophila pneumoniae in vitro has been shown to be toll-like receptor (TLR2)-dependent, but TLR4 is also involved to a minor extent. To investigate the role of TLR2 and TLR4 in vivo, a murine model of C. pneumoniae infection was established. Mice were infected intranasally with a low inoculum of 106 C. pneumoniae elementary bodies (EB) and spreading of bacteria was monitored by real-time PCR. The bronchoalveolar lavage (BAL) showed maximal bacterial load on the day of infection and the lung 2 days later. By day 95, C. pneumoniae were eradicated completely. In serum, anti-C. pneumoniae IgG became detectable on day 18 by microimmunofluorescence test. The course of infection was mild with no apparent symptoms, lack of acute phase response and no induction of tumor necrosis factor-alpha and interleukin-6 in BAL, lung supernatants or blood. Infection of TLR2-/- and C3H/HeJ mice revealed no differences in clearance of bacteria and serological responses compared to wild-type controls, even if a dose of 10(7) EB was used. Intracellular replication of C. pneumoniae in the lungs was proven by the efficacy of antibiotic treatment. These findings indicate that in vivo TLR2 and TLR4 are not important for the development of antibodies and elimination of C. pneumoniae.
Mueller
Markus
M
Biochemical Pharmacology, University of Konstanz, Konstanz 78457, Germany.
Postius
Stefan
S
Thimm
Jean G
JG
Gueinzius
Katja
K
Muehldorfer
Inge
I
Hermann
Corinna
C
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D017963:Azithromycin / Q000494:pharmacology / Q000627:therapeutic use; D018893:Bronchoalveolar Lavage; D023521:Chlamydophila Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D016993:Chlamydophila pneumoniae / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification; D005260:Female; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D008168:Lung / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D015846:Monokines / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D015846:Monokines; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D017963:Azithromycin; D012293:Rifampin