Role of p38 and Early Growth Response Factor 1 in the Macrophage Response to Group B Streptococcus
| Autor: | Katherine A. Fitzgerald, Shizuo Akira, Sachin D. Deshmukh, Sandra Santos-Sierra, Egil Lien, Philipp Henneke, Sybille Kenzel, Inga Moeller, Bilge Ergin, Douglas T. Golenbock |
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| Rok vydání: | 2009 |
| Předmět: |
TIRAP
Chemokine medicine.medical_treatment Immunology Biology Models Biological p38 Mitogen-Activated Protein Kinases Microbiology Cell Line Streptococcus agalactiae Mice medicine Animals Cells Cultured Early Growth Response Protein 1 ets-Domain Protein Elk-1 Mice Knockout Host Response and Inflammation Mice Inbred C57BL Transcription Factor AP-1 TLR2 Infectious Diseases Cytokine TRIF Myeloid Differentiation Factor 88 Macrophages Peritoneal TLR4 biology.protein Cytokines Parasitology Tumor necrosis factor alpha |
| Zdroj: | Infection and Immunity. 77:2474-2481 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | Group B streptococcus (GBS), the most frequent single isolate in neonatal sepsis and meningitis, potently activates inflammatory macrophage genes via myeloid differentiation antigen 88 (MyD88). However, events parallel to and downstream of MyD88 that instruct the macrophage response are incompletely understood. In this study, we found that only MyD88, not the Toll-like receptor (TLR) adapter proteins MAL/TIRAP, TRIF, and TRAM, essentially mediates the cytokine (tumor necrosis factor [TNF] and interleukin-6) and chemokine (RANTES) responses to whole GBS organisms, although MAL, TRIF, and TRAM have been shown to mediate the responses to substructures in other gram-positive and gram-negative bacteria. GBS-induced, MyD88-dependent phosphorylation of the mitogen-activated protein kinase p38 activated the transcription factor AP-1 and early growth response factor 1 (Egr-1) but not NF-κB. Furthermore, phosphorylation of Ets-like molecule 1 (Elk-1) was mediated by p38. However, in contrast to Egr-1 and AP-1, Elk-1 was dispensable for transcriptional activation of TNF by GBS organisms. Studies of macrophages from Elk-1-deficient mice revealed that Elk-1 was furthermore nonessential for the TNF responses to purified TLR2 and TLR4 agonists, which was in notable contrast to what was revealed in studies employing in vitro expression systems. In conclusion, MyD88, p38, and Egr-1, but not Elk-1, essentially mediate the inflammatory cytokine response to GBS organisms. |
| Databáze: | OpenAIRE |
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