IL-10 suppresses T cell expansion while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus macaques

by Christine E. Nelson, Taylor W. Foreman, Eduardo R. Fukutani, Keith D. Kauffman, Shunsuke Sakai, Joel D. Fleegle, Felipe Gomez, NIAID/DIR Tuberculosis Imaging Program , Sydnee T. Gould, Cyril Le Nouën, Xueqiao Liu, Tracey L. Burdette, Nicole L. Garza, Bernard A. P. Lafont, Kelsie Brooks, Cecilia S. Lindestam Arlehamn, Daniela Weiskopf, Alessandro Sette, Heather D. Hickman, Ursula J. Buchholz, Reed F. Johnson, Jason M. Brenchley, James P. Oberman, Artur T. L. Quieroz, Bruno B. Andrade, Laura E. Via, Daniel L. Barber

The regulation of inflammatory responses and pulmonary disease during SARS-CoV-2 infection is incompletely understood. Here we examine the roles of the prototypic pro- and anti-inflammatory cytokines IFNγ and IL-10 using the rhesus macaque model of mild COVID-19. We find that IFNγ drives the development of ¹⁸fluorodeoxyglucose (FDG)-avid lesions in the lungs as measured by PET/CT imaging but is not required for suppression of viral replication. In contrast, IL-10 limits the duration of acute pulmonary lesions, serum markers of inflammation and the magnitude of virus-specific T cell expansion but does not impair viral clearance. We also show that IL-10 induces the subsequent differentiation of virus-specific effector T cells into CD69⁺CD103⁺ tissue resident memory cells (Trm) in the airways and maintains Trm cells in nasal mucosal surfaces, highlighting an unexpected role for IL-10 in promoting airway memory T cells during SARS-CoV-2 infection of macaques.