PLoS Pathogens (Jul 2024)

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

  • 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

DOI
https://doi.org/10.1371/journal.ppat.1012339
Journal volume & issue
Vol. 20, no. 7
p. e1012339

Abstract

Read online

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.