ABSTRACT
The roles of Toll-like receptor (TLR) 2 and TLR4 in the host inflammatory response to infection caused by Chlamydia trachomatis have not been elucidated. We examined production of TNF-alpha and IL-6 in wild-type TLR2 knockout (KO), and TLR4 KO murine peritoneal macrophages infected with the mouse pneumonitis strain of C. trachomatis. Furthermore, we compared the outcomes of genital tract infection in control, TLR2 KO, and TLR4 KO mice. Macrophages lacking TLR2 produced significantly less TNF-alpha and IL6 in response to active infection. In contrast, macrophages from TLR4 KO mice consistently produced higher TNF-alpha and IL-6 responses than those from normal mice on in vitro infection. Infected TLR2-deficient fibroblasts had less mRNA for IL-1, IL-6, and macrophage-inflammatory protein-2, but TLR4-deficient cells had increased mRNA levels for these cytokines compared with controls, suggesting that ligation of TLR4 by whole chlamydiae may down-modulate signaling by other TLRs. In TLR2 KO mice, although the course of genital tract infection was not different from that of controls, significantly lower levels of TNF-alpha and macrophage-inflammatory protein-2 were detected in genital tract secretions during the first week of infection, and there was a significant reduction in oviduct and mesosalpinx pathology at late time points. TLR4 KO mice responded to in vivo infection similarly to wild-type controls and developed similar pathology. TLR2 is an important mediator in the innate immune response to C. trachomatis infection and appears to play a role in both early production of inflammatory mediators and development of chronic inflammatory pathology.
Subject(s)
Chlamydia Infections/immunology , Chlamydia trachomatis , Fallopian Tubes/pathology , Genital Diseases, Female/immunology , Membrane Glycoproteins/physiology , Receptors, Cell Surface/physiology , Animals , Antibodies, Bacterial/blood , Cells, Cultured , Chemokine CXCL2 , Chemokines/genetics , Chemokines/metabolism , Chlamydia Infections/genetics , Chlamydia Infections/pathology , Down-Regulation/genetics , Down-Regulation/immunology , Fallopian Tubes/immunology , Female , Fibroblasts/immunology , Fibroblasts/microbiology , Fibroblasts/pathology , Genital Diseases, Female/genetics , Genital Diseases, Female/pathology , Immunoglobulin G/blood , Interleukin-1/genetics , Interleukin-1/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Lung/immunology , Lung/microbiology , Lung/pathology , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/metabolism , Membrane Glycoproteins/deficiency , Membrane Glycoproteins/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Pneumonia/genetics , Pneumonia/immunology , RNA, Messenger/antagonists & inhibitors , RNA, Messenger/metabolism , Receptors, Cell Surface/deficiency , Receptors, Cell Surface/genetics , Toll-Like Receptor 2 , Toll-Like Receptor 4 , Toll-Like Receptors , Tumor Necrosis Factor-alpha/metabolismABSTRACT
In this study, we reviewed cases of invasive disease due to nontypeable Haemophilus influenzae among children hospitalized at Arkansas Children's Hospital from 1993 to 2001. A total of 28 cases were examined, including 21 associated with bacteremia and 4 associated with meningitis. Of the patients examined, 86% were
