Abstract:
BACKGROUND:Toll-like receptor 2 (TLR2) plays a critical role in mediating inflammatory/immune responses against bacterial pathogens in lung. Streptococcus pneumoniae (S. pneumoniae) and nontypeable Haemophilus influenzae (NTHi) were previously reported to synergize with each other to induce inflammatory responses. Despite the relatively known intracellular signaling pathways involved in the synergistic induction of inflammation, it is still unclear if both bacterial pathogens also synergistically induce expression of surface TLR2. RESULTS:Here we provide direct evidence that S. pneumoniae synergizes with NTHi to upregulate TLR2 expression in lung and middle ear of the mice. Pneumolysin (PLY) appears to be the major virulence factor involved in this synergism. Moreover, S. pneumoniae PLY induces TLR2 expression via a TLR4-MyD88-NF-kappaB-dependent signaling pathway. Interestingly, tumor suppressor CYLD acts as a negative regulator of S. pneumoniae-induced TLR2 up-regulation via negative-crosstalk with NF-kappaB signaling. CONCLUSION:Our study thus provides novel insights into the regulation of TLR2 expression in mixed bacterial infections.
journal_name
BMC Immunoljournal_title
BMC immunologyauthors
Lim JH,Ha U,Sakai A,Woo CH,Kweon SM,Xu H,Li JDdoi
10.1186/1471-2172-9-40subject
Has Abstractpub_date
2008-07-29 00:00:00pages
40issn
1471-2172pii
1471-2172-9-40journal_volume
9pub_type
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