NK Cell Responses in Zika Virus Infection Are Biased towards Cytokine-Mediated Effector Functions

Abstract

Zika virus (ZIKV) is a mosquito-borne flavivirus that has emerged as a global concern because of its impact on human health. ZIKV infection during pregnancy can cause microcephaly and other severe brain defects in the developing fetus and there have been reports of the occurrence of Guillain-Barré syndrome in areas affected by ZIKV. NK cells are activated during acute viral infections and their activity contributes to a first line of defense because of their ability to rapidly recognize and kill virus-infected cells. To provide insight into NK cell function during ZIKV infection, we have profiled, using mass cytometry, the NK cell receptor-ligand repertoire in a cohort of acute ZIKV-infected female patients. Freshly isolated NK cells from these patients contained distinct, activated, and terminally differentiated, subsets expressing higher levels of CD57, NKG2C, and KIR3DL1 as compared with those from healthy donors. Moreover, KIR3DL1+ NK cells from these patients produced high levels of IFN-γ and TNF-α, in the absence of direct cytotoxicity, in response to in vitro stimulation with autologous, ZIKV-infected, monocyte-derived dendritic cells. In ZIKV-infected patients, overproduction of IFN-γ correlated with STAT-5 activation (r = 0.6643; p = 0.0085) and was mediated following the recognition of MHC class 1–related chain A and chain B molecules expressed by ZIKV-infected monocyte-derived dendritic cells, in synergy with IL-12 production by the latter cells. Together, these findings suggest that NK cells contribute to the generation of an efficacious adaptive anti-ZIKV immune response that could potentially affect the outcome of the disease and/or the development of persistent symptoms.

Costimulatory CD226 Signaling Regulates Proliferation of Memory-like NK Cells in Healthy Individuals with Latent Mycobacterium tuberculosis Infection

“…Initially recognized as part of a stereotyped innate immune mechanism, several reports have clearly shown that NK cells can acquire memory characteristics [ 6 , 7 , 8 , 9 ]. A role of memory-like NK cells (mlNKs) has been shown for cytomegalovirus [ 7 , 10 ], Zika virus [ 11 , 12 ], simian-human immunodeficiency virus (SHIV) [ 13 ], HIV [ 14 ], flu virus [ 15 , 16 ] as well as tuberculosis (TB) [ 17 , 18 ]. NK memory has also been reported against haptens [ 6 ] as well as a combination of IL12, IL15 and IL18 cytokines [ 8 , 9 ].…”