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PLoS One. 2009;4(1):e4127. doi: 10.1371/journal.pone.0004127. Epub 2009 Jan 5.

Toll-like receptor 3 signaling on macrophages is required for survival following coxsackievirus B4 infection.

Author information

1
Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

Toll-like receptor 3 (TLR3) has been proposed to play a central role in the early recognition of viruses by sensing double stranded RNA, a common intermediate of viral replication. However, several reports have demonstrated that TLR3 signaling is either dispensable or even harmful following infection with certain viruses. Here, we asked whether TLR3 plays a role in the response to coxsackievirus B4 (CB4), a prevalent human pathogen that has been associated with pancreatitis, myocarditis and diabetes. We demonstrate that TLR3 signaling on macrophages is critical to establish protective immunity to CB4. TLR3 deficient mice produced reduced pro-inflammatory mediators and are unable to control viral replication at the early stages of infection resulting in severe cardiac damage. Intriguingly, the absence of TLR3 did not affect the activation of several key innate and adaptive cellular effectors. This suggests that in the absence of TLR3 signaling on macrophages, viral replication outpaces the developing adaptive immune response. We further demonstrate that the MyD88-dependent signaling pathways are not only unable to compensate for the loss of TLR3, they are also dispensable in the response to this RNA virus. Our results demonstrate that TLR3 is not simply part of a redundant system of viral recognition, but rather TLR3 plays an essential role in recognizing the molecular signatures associated with specific viruses including CB4.

PMID:
19122812
PMCID:
PMC2606033
DOI:
10.1371/journal.pone.0004127
[Indexed for MEDLINE]
Free PMC Article

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