unconventional repertoire profile is imprinted during acute chikungunya infection for natural killer cells polarization toward cytotoxicity非传统的曲目配置文件是印在急性感染基孔肯雅热自然杀伤细胞极化细胞毒性.pdf

Unconventional Repertoire Profile Is Imprinted during Acute Chikungunya Infection for Natural Killer Cells Polarization toward Cytotoxicity 1,2. 3,4. 1,2,3. ´ 1,2 ´ 1,2 Caroline Petitdemange , Pierre Becquart , Nadia Wauquier , Vivien Beziat , Patrice Debre , Eric M. Leroy3,4, Vincent Vieillard1,2* ´ ˆ ´ ˆ ` ´ ´ 1 INSERM UMR-S 945, Immunite et Infection, Hopital Pitie-Salpetriere, Paris, France, 2 Universite Pierre et Marie Curie, Paris, France, 3 Unite des Maladies Virales ´ Emergentes, Centre International de Recherches Medicales de Franceville, Franceville, Gabon, 4 UMR 224 IRD/CNRS/UM1, Montpellier, France Abstract Chikungunya virus (CHIKV) is a worldwide emerging pathogen. In humans it causes a syndrome characterized by high fever, polyarthritis, and in some cases lethal encephalitis. Growing evidence indicates that the innate immune response plays a role in controlling CHIKV infection. We show here that CHIKV induces major but transient modifications in NK-cell phenotype and function soon after the onset of acute infection. We report a transient clonal expansion of NK cells that coexpress CD94/NKG2C and inhibitory receptors for HLA-C1 alleles and are correlated with the viral load. Functional tests reveal cytolytic capacity driven by NK cells in the absence of exogenous signals and severely impaired IFN-c production. Collectively these data provide insight into the role of this unique subset of