Toll-like receptor–mediated activation of neutrophils by influenza A virus

Jennifer P. Wang, et al. Blood 112: 2028-2034(2008)

Speaker: Chih-Yuan Kuo (郭芝源)                                 Time: 14:00~15:00, Nov. 19, 2008

Commentator: Dr. Chun-Keung Yu (余俊強老師)          Place: Room 601

Abstract:

    Influenza A virus, a membrane of the family Orthomyxoviridae, is a negative stranded RNA virus which infects epithelial cells of the upper respiratory tract and bronchi. During influenza A virus infection, neutrophils are involved in the initial host response to infection and may contribute to the pathogenesis of severe infection. Toll-like receptors（TLRs）play critical roles as pattern-recognition receptors (PRR). Neutrophils express TLR1, 2, 4, 5, 6, 7, 8, 9, and 10—all the TLRs except TLR3¹. TLR7 and TLR8 are closely related endosomal receptors that recognize single-stranded RNA². In pervious studies, influenza A virus induced the production of inflammatory cytokines in a TLR7-dependent manner and viral RNA is a potent inducer of TLR7 response in several cell systems. Thus, the authors tried to elucidate whether TLR7 and TLR8 on neutrophils contribute to inflammatory cytokine responses to influenza virus. They found both TLR ligands and influenza A viral RNA induced inflammatory cytokine production by neutrophils. Moreover, both TLR7 and TLR8 could be activated by viral RNA. In addition, influenza virus entry and endosomal acidification was required for neutrophil activation and cytokine production. In vivo, murine neutrophil cytokine responses to influenza virus also required TLR7 signaling. In conclusion, the authors demonstrated neutrophil activation by influenza virus and highlight the importance of

TLR7 and TLR8 in the response.

References:

1. Hayashi F, Means TK, Luster AD. 2003. Toll-like receptors stimulate human neutrophil function. Blood 102:2660-2669.

2. Diebold SS, et al. 2004. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303:1529-1531