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https://www.arca.fiocruz.br/handle/icict/50070
NK CELL RESPONSES IN ZIKA VIRUS INFECTION ARE BIASED TOWARDS CYTOKINE-MEDIATED EFFECTOR FUNCTIONS
Infecção por Zika virus
Microcefalia
Flavivirus
Células Dendríticas
Author
Affilliation
Sorbonne Universite. Inserm. Centre d’Immunologie et des Maladies Infectieuses. Paris, France.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
Univ Paris. Faculté de Medecine Pierre et Marie Curie. Plateforme de Cytometrie. Site Pitie-Salpêtriere. Paris, France.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
Sorbonne Universite. Inserm. Centre d’Immunologie et des Maladies Infectieuses. Paris, France.
Sorbonne Universite. Inserm. Centre d’Immunologie et des Maladies Infectieuses. Paris, France.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Secretaria de Saúde da Bahia. Salvador, BA, Brasil.
Sorbonne Universite. Inserm. Centre d’Immunologie et des Maladies Infectieuses. Paris, France.
Univ Paris. Faculté de Medecine Pierre et Marie Curie. Plateforme de Cytometrie. Site Pitie-Salpêtriere. Paris, France.
Sorbonne Universite. Inserm. Centre d’Immunologie et des Maladies Infectieuses. Paris, France.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
Sorbonne Universite. Inserm. Centre d’Immunologie et des Maladies Infectieuses. Paris, France.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
Univ Paris. Faculté de Medecine Pierre et Marie Curie. Plateforme de Cytometrie. Site Pitie-Salpêtriere. Paris, France.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
Sorbonne Universite. Inserm. Centre d’Immunologie et des Maladies Infectieuses. Paris, France.
Sorbonne Universite. Inserm. Centre d’Immunologie et des Maladies Infectieuses. Paris, France.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Secretaria de Saúde da Bahia. Salvador, BA, Brasil.
Sorbonne Universite. Inserm. Centre d’Immunologie et des Maladies Infectieuses. Paris, France.
Univ Paris. Faculté de Medecine Pierre et Marie Curie. Plateforme de Cytometrie. Site Pitie-Salpêtriere. Paris, France.
Sorbonne Universite. Inserm. Centre d’Immunologie et des Maladies Infectieuses. Paris, France.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
Sorbonne Universite. Inserm. Centre d’Immunologie et des Maladies Infectieuses. Paris, France.
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-Barr e 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-g and
TNF-a, 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-g correlated with STAT-5 activation (r 5 0.6643; p 5 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.
Keywords in Portuguese
Zika virusInfecção por Zika virus
Microcefalia
Flavivirus
Células Dendríticas
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