Streptococcus pneumoniae synergizes with nontypeable Haemophilus influenzae to induce inflammation via upregulating TLR2

Jae Hyang Lim, Unhwan Ha, Akihiro Sakai, Chang Hoon Woo, Soo Mi Kweon, Haidong Xu, Jian Dong Li

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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-κB-dependent signaling pathway. Interestingly, tumor suppressor CYLD acts as a negative regulator of S. pneumoniae-induced TLR2 up-regulation via negative-crosstalk with NF-κB signaling. Conclusion: Our study thus provides novel insights into the regulation of TLR2 expression in mixed bacterial infections.

Original languageEnglish
Article number40
JournalBMC Immunology
Volume9
DOIs
StatePublished - 29 Jul 2008

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