Myeloid differentiation factor 88-dependent signalling controls bacterial growth during colonization and systemic pneumococcal disease in mice.
The Toll-like receptors (TLRs) and the myeloid differentiation factor 88 (MyD88) are key players in the activation of the innate immune defence during microbial infections. Using different murine infection models, we show that MyD88-dependent signalling is crucial for the activation of the innate immune defence against Streptococcus pneumoniae. Our data demonstrate that both local and systemic inflammatory response to S. pneumoniae depends on the presence of MyD88 to clear bacterial colonization of the upper respiratory tract and to prevent pulmonary and systemic infection in mice. Finally, we described a strong correlation between enhanced bacterial growth in the bloodstream of MyD88-deficient mice and the inability to lower the serum iron concentration in response to infection.
Albiger
Barbara
B
SMITTSKYDDSINSTITUTET, Swedish Institute for Infectious Disease Control, Karolinska Institutet, Solna, 171 77 Stockholm, Sweden. Barbara.Albiger@mtc.ki.se
Sandgren
Andreas
A
Katsuragi
Hiroaki
H
Meyer-Hoffert
Ulf
U
Beiter
Katharina
K
Wartha
Florian
F
Hornef
Mathias
M
Normark
Staffan
S
Normark
Birgitta Henriques
BH
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D016470:Bacteremia / Q000276:immunology / Q000382:microbiology; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88; D009305:Nasopharynx / Q000382:microbiology; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology*; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000254:growth & development* / Q000472:pathogenicity*; D014132:Trachea / Q000382:microbiology
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic