Role of p38 and early growth response factor 1 in the macrophage response to group B streptococcus
Authors
Kenzel, SybilleSantos-Sierra, Sandra
Deshmukh, Sachin D.
Moeller, Inga
Ergin, Bilge
Fitzgerald, Katherine A.
Lien, Egil
Akira, Shizuo
Golenbock, Douglas T.
Henneke, Phillip
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2009-04-01Keywords
AnimalsCell Line
Cells, Cultured
Cytokines
Early Growth Response Protein 1
Macrophages, Peritoneal
Mice
Mice, Inbred C57BL
Mice, Knockout
Models, Biological
Myeloid Differentiation Factor 88
Streptococcus agalactiae
Transcription Factor AP-1
ets-Domain Protein Elk-1
p38 Mitogen-Activated Protein Kinases
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
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-kappaB. 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.Source
Infect Immun. 2009 Jun;77(6):2474-81. Epub 2009 Mar 30. Link to article on publisher's siteDOI
10.1128/IAI.01343-08Permanent Link to this Item
http://hdl.handle.net/20.500.14038/35229PubMed ID
19332535Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/IAI.01343-08