The dynamics of γδ T cell responses in nonhuman primates during SARS-CoV-2 infection.
Alyssa C FearsEdith M WalkerNicole ChirichellaNadia SlisarenkoKristen M MerinoNadia GoldenBreanna PicouSkye SpencerKasi E Russell-LodrigueLara A Doyle-MeyersRobert V BlairBrandon J BeddingfieldNicholas J ManessChad J RoyNamita RoutPublished in: Communications biology (2022)
Although most SARS-CoV-2 infections are mild, some patients develop systemic inflammation and progress to acute respiratory distress syndrome (ARDS). However, the cellular mechanisms underlying this spectrum of disease remain unclear. γδT cells are T lymphocyte subsets that have key roles in systemic and mucosal immune responses during infection and inflammation. Here we show that peripheral γδT cells are rapidly activated following aerosol or intra-tracheal/intra-nasal (IT/IN) SARS-CoV-2 infection in nonhuman primates. Our results demonstrate a rapid expansion of Vδ1 γδT cells at day1 that correlate significantly with lung viral loads during the first week of infection. Furthermore, increase in levels of CCR6 and Granzyme B expression in Vδ1 T cells during viral clearance imply a role in innate-like epithelial barrier-protective and cytotoxic functions. Importantly, the early activation and mobilization of circulating HLA-DR + CXCR3 + γδT cells along with significant correlations of Vδ1 T cells with IL-1Ra and SCF levels in bronchoalveolar lavage suggest a novel role for Vδ1 T cells in regulating lung inflammation during aerosol SARS-CoV-2 infection. A deeper understanding of the immunoregulatory functions of MHC-unrestricted Vδ1 T cells in lungs during early SARS-CoV-2 infection is particularly important in the wake of emerging new variants with increased transmissibility and immune evasion potential.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- acute respiratory distress syndrome
- immune response
- extracorporeal membrane oxygenation
- mechanical ventilation
- oxidative stress
- end stage renal disease
- dendritic cells
- coronavirus disease
- chronic kidney disease
- poor prognosis
- newly diagnosed
- ejection fraction
- rheumatoid arthritis
- peritoneal dialysis
- systemic lupus erythematosus
- climate change
- regulatory t cells
- intensive care unit
- binding protein
- randomized controlled trial
- toll like receptor
- disease activity
- dna methylation
- ulcerative colitis
- sensitive detection
- chronic rhinosinusitis
- interstitial lung disease