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Войти в исследования Science translational medicine · 2023
Malaria-driven expansion of adaptive-like functional CD56-negative NK cells correlates with clinical immunity to malaria.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Ty Maureen, Sun Shenghuan, Callaway Perri C, Rek John, Press Kathleen D, van der Ploeg Kattria, Nideffer Jason, Hu Zicheng, Klemm Sandy, Greenleaf William, Donato Michele, Tukwasibwe Stephen, Arinaitwe Emmanuel, Nankya Felistas, Musinguzi Kenneth, Andrew Dean, de la Parte Lauren, Mori Diego Martinez, Lewis Savannah N, Takahashi Saki, Rodriguez-Barraquer Isabel, Greenhouse Bryan, Blish Catherine, Utz P J, Khatri Purvesh, Dorsey Grant, Kamya Moses, Boyle Michelle, Feeney Margaret, Ssewanyana Isaac, Jagannathan Prasanna
Аннотация
Natural killer (NK) cells likely play an important role in immunity to malaria, but the effect of repeated malaria on NK cell responses remains unclear. Here, we comprehensively profiled the NK cell response in a cohort of 264 Ugandan children. Repeated malaria exposure was associated with expansion of an atypical, CD56neg population of NK cells that differed transcriptionally, epigenetically, and phenotypically from CD56dim NK cells, including decreased expression of PLZF and the Fc receptor γ-chain, increased histone methylation, and increased protein expression of LAG-3, KIR, and LILRB1. CD56neg NK cells were highly functional and displayed greater antibody-dependent cellular cytotoxicity than CD56dim NK cells. Higher frequencies of CD56neg NK cells were associated with protection against symptomatic malaria and high parasite densities. After marked reductions in malaria transmission, frequencies of these cells rapidly declined, suggesting that continuous exposure to Plasmodium falciparum is required to maintain this modified, adaptive-like NK cell subset.