Monocytes and macrophages limit systemic infection and modulate the CD4 T cell response during Zika virus infection in mice

Abstract

Abstract Monocytes and macrophages are antiviral innate immune effector cells that also serve as cellular hosts of Zika virus (ZIKV). To investigate the precise role of monocytes and macrophages during ZIKV infection in vivo, monocytes and macrophages were depleted with clodronate liposomes before ZIKV infection in wild-type C57BL/6 mice, and viral burden and ZIKV-specific immune responses were assessed. Chlodronate liposometreated mice had higher level of ZIKV RNA in the serum and spleen relative to control liposome-treated mice at early time points after infection. At later time points after infection, chlodronate liposome-treated mice developed an impaired ZIKV-specific Th1 response in terms of both magnitude and quality, whereas they exhibited enhanced Tfh, germinal center B cell, plasma cell, and neutralizing antibody responses as compared to control liposome-treated mice. These data indicate that monocytes and macrophages limit ZIKV dissemination and regulate the balance between Th1 versus Tfh responses during ZIKV infection. Thus, monocytes and macrophages contribute to both the innate control of ZIKV infection and regulation of the adoptive immune response.