Innate Immunity Modulation during Zika Virus Infection on Pregnancy: What We Still Need to Know for Medical Sciences Breakthrough

Abstract

Zika virus (ZIKV), an arthropod-borne flavivirus, was classified as reemerging infectious disease and included as neglected tropical disease. During the recent ZIKV outbreak in South America, it has been demonstrated that ZIKV infection during pregnancy is strongly associated with fetal loss, malformations and neurological disorders in newborns. Despite the first line of host immune defense is related to innate immunity activation, the immunological homeostasis is essential for pregnancy success. Although the dynamic changes in maternal-fetal immunity is not completely understood and poorly investigated, the knowledge of immune responses during gestation is very important for infectious disease prevention and control, as ZIKV. Here, we put together more and new information about the innate immunity during gestation, highlighting three parts probably involved with clinical outcome and/or not well explored in literature: 1) type III interferon; 2) innate regulatory cells; and 3) cell death pathways modulation. Additionally, we will be focused on discussing how the dynamic responses of innate immune system during pregnancy and its effects in newborns, could be modulated by ZIKV, as well as how efforts on development of new/old drugs and vaccines could be effective for ZIKV prevention and control to provide a successful pregnancy.

Neutrophil Recruitment and Participation in Severe Diseases Caused by Flavivirus Infection

“…Neutrophils express high levels of the heterodimeric IFN-λ receptor IFNLR1/IL10RB [ 166 ], resulting in a repressed state of neutrophils’ effector functions induced by type-III IFN signaling, exemplified by reduction in neutrophil infiltration, degranulation, ROS production and NETs release [ 167 ]. In the early stages of ZIKV placental infection, typical flavivirus antagonism of IFN responses result in downregulation of IFN-λ2, leading to an aberrant neutrophil response and CZS [ 168 ]. CZS is later accompanied by a strong type-I IFN response, increased expression of IFIT5 and decrease of ISG15 mRNA expression levels [ 169 ].…”