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Exposure to lung-migrating helminth protects against murine SARS-CoV-2 infection through macrophage-dependent T cell activation.

Oyebola O OyesolaKerry L HilliganSivaranjani NamasivayamNina HowardChad S ClancyMingming ZhaoSandra D OlandKasalina N KiwanukaNicole L GarzaBernard A P LafontReed F JohnsonKatrin D Mayer-BarberAlan SherP'ng Loke
Published in: Science immunology (2023)
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.
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