Exposure to lung-migrating helminth protects against murine SARS-CoV-2 infection through macrophage-dependent T cell activation
Oyebola O. Oyesola, Kerry L. Hilligan, Sivaranjani Namasivayam, Nina Howard, Chad S. Clancy, Mingming Zhao, Sandra D. Oland, Kasalina N. Kiwanuka, Nicole L. Garza, Bernard A. P. Lafont, Reed F. Johnson, Katrin D. Mayer-Barber, Alan Sher, P’ng Loke
Abstract
Helminth endemic regions report lower COVID-19 morbidity and mortality. Here, we show that lung remodeling from a prior infection with a lung-migrating helminth, Nippostrongylus brasiliensis , enhances viral clearance and survival of human-ACE2 transgenic mice challenged with SARS-CoV-2 (SCV2). This protection is associated with a lymphocytic infiltrate, including increased accumulation of pulmonary SCV2-specific CD8 + T cells, and anti-CD8 antibody depletion abrogated the N. brasiliensis– mediated reduction in viral loads. Pulmonary macrophages with a type 2 transcriptional and epigenetic signature persist in the lungs of N. brasiliensis –exposed mice after clearance of the parasite and establish a primed environment for increased CD8 + T cell recruitment and activation. Accordingly, depletion of macrophages ablated the augmented viral clearance and accumulation of CD8 + T cells driven by prior N. brasiliensis infection. Together, these findings support the concept that lung-migrating helminths can limit disease severity during SCV2 infection through macrophage-dependent enhancement of antiviral CD8 + T cell responses.