Neutrophil Extracellular Traps Mediate a Host Defense Response to Human Immunodeficiency Virus-1

Tatsuya Saitoh et al. Cell Host Microbe. (2012) 12, 109–116.

Speaker: Yi-Pin Tsai (蔡佾頻)                                       Time: 15:00~16:00, Jan 2, 2013

Commentator: Dr. Chung-Hsin Tseng (曾忠信)           Place: Room601

Abstract

In previous studies, neutrophils have been shown to defend against invading microbes by two strategies known as phagocytosis and degranulation. In addition, recent studies reveal that neutrophils release the neutrophil extracellular trap (NET) to prevent the spreading of bacteria and fungi. However, the role of NET in antiviral responses remains unclear. Myeloperoxidase (MPO) and α-defensin bound on NET have been reported to inactivate human immunodeficiency virus-1 (HIV-1). Therefore in the present study, the role of NET in the elimination of HIV-1 was examined. The authors showed that HIV-1 was captured by NET, and the infectivity of the virus was reduced by MPO and α-defensin. To investigate whether HIV-1 infection induces NET formation, they used different strains of HIV-1 to stimulate neutrophils. They found that Toll-like receptor (TLR) 7 and TLR8 triggered NET formation by stimulating the production of reactive oxygen species through the mitogen-activated protein kinase pathway. Interestingly, neutrophils are rich in mucosal tissues which are the major routes of HIV-1 entry, but fail to inhibit HIV-1 dissemination in the host. Therefore, the authors further investigated how HIV-1 escapes from the NET-dependent antiviral response. They found that CD209⁺ dendritic cells sensed HIV-1 envelope glycoprotein and subsequently secreted interleukin-10, an immunosuppressive cytokine. Interleukin-10 suppressed NET formation by blocking the activation of TLR7 and TLR8 signaling. In conclusion, TLR7 and TLR8 mediate HIV-1 elimination by inducing NET formation. MPO and α-defensin expressed on NET reduced the infectivity of HIV-1. However, HIV-1 escapes this antiviral response by inducing CD209-dependent interleukin-10 production by dendritic cells.

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