The activation of complement C5a-C5aR1 axis in astrocytes facilitates the neuropathogenesis due to EV-A71 infection by upregulating CXCL1

Abstract

Enterovirus A71 (EV-A71) is a common small RNA virus with highly neuroinvasive tendencies. Our previous studies took the view that EV-A71 could infect astrocytes and result in complement activation in vivo . We investigated how complement interacts with astrocytes to promote a severe inflammatory response upon EV-A71 infection in the study. As expected, our data demonstrate that EV-A71 triggers robust activation of the C5a–C5aR1 axis in astrocytes and that knockout or blockade of C5aR1 in animals exposed to lethal doses of EV-A71 significantly enhances survival by diminishing the production of the chemokines CXCL1 and IL-6. In addition, neutralizing CXCL1 significantly alleviates the neuropathogenesis caused by EV-A71 infection. Thus, inhibiting the C5a–C5aR1 axis has emerged as a potential therapeutic strategy to mitigate neural damage caused by EV-A71 infection.