Memory-like NK responses to Zika virus infection

Abstract

Abstract The formation of memory is a hallmark feature of adaptive immune cells such as T and B lymphocytes. Natural killer cells (NK), though part of the innate immunity, have also been shown to undergo memory program to haptens, cytomegalovirus and other pathogens. We investigated NK response after Zika virus infection in mice. The activation of NK cells was evident early after infection, with increased frequencies of CD27+KLRG1+ NK cells producing higher amount of IFN-γ and perforin. These responses were normalized a month post infection. However, investigating CD27+ NK cells a month post Zika infection led to identification of memory like phenotype in these cells. The CD27+ NK subset (day 37 post infection) demonstrated greater therapeutic potential than CD27− NK subset or naive CD27+ NK cells when adoptively transferred to Zika infected interferon receptor deficient mice. The cell trace violet labeled CD27+ NK cells (day 37 post infection) when transferred to recipient mice robustly proliferated after Zika challenge. Moreover, the response of these memory-like CD27+ NK cells were antigen specific as these cells failed to proliferate in the recipient mice after bacterial challenge. Memory-like CD27+ NK cells persisted, had lesser reactive oxygen species, healthy mitochondria and lesser apoptotic features. This study reveals memory-like NK responses to Zika virus infection. It remains to be seen if specific NK receptor or cytokines are involved in generation of memory-like NK responses to Zika infection.