Cell reports · 2025
Phagosomal RNA sensing through TLR8 controls susceptibility to tuberculosis.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Maserumule Charlotte, Passemar Charlotte, Oh Olivia S H, Hegyi Kriztina, Brown Karen, Weimann Aaron, Dinan Adam, Davila Sonia, Klapholz Catherine, Bryant Josephine, Verma Deepshikha, Gadwa Jacob, Krishnananthasivam Shivankari, Vongtongsalee Kridakorn, Kendall Edward, Trelles Andres, Hibberd Martin L, Sanz Joaquín, Bertol Jorge, Vázquez-Iniesta Lucia, Andi Kaliappan, Kumar S Siva, Ordway Diane, Prados-Rosales Rafael, MacAry Paul A, Floto R Andres
Аннотация
Genetic determinants of susceptibility to Mycobacterium tuberculosis (Mtb) remain poorly understood but could provide insights into critical pathways involved in infection, informing host-directed therapies and enabling risk stratification at individual and population levels. Through a genome-wide forward genetic screen, we identify Toll-like receptor 8 (TLR8) as a key regulator of intracellular killing of Mtb. Pharmacological TLR8 activation enhances the killing of phylogenetically diverse clinical isolates of drug-susceptible and multidrug-resistant Mtb by macrophages and during in vivo infection in mice. TLR8 is activated by phagosomal mycobacterial RNA released by extracellular membrane vesicles and enhances xenophagy-dependent Mtb killing. We find that the TLR8 variant M1V, common in Far Eastern populations, enhances intracellular killing of Mtb through preferential signal-dependent trafficking to phagosomes. TLR8 signaling may, therefore, both regulate susceptibility to tuberculosis and provide novel drug targets.