Helminth exposure protects against murine SARS-CoV-2 infection through macrophage dependent T cell activation

• Published in: bioRxiv
• Main Authors: Hilligan, Kerry L, Oyesola, Oyebola O, Namasivayam, Sivaranjani, Howard, Nina, Clancy, Chad S, Oland, Sandra D, Garza, Nicole L, Lafont, Bernard A P, Johnson, Reed F, Mayer-Barber, Katrin D, Sher, Alan, Loke, P'ng
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 10.11.2022
• Subjects: ACE2; Angiotensin-converting enzyme 2; Antigen presentation; Antiviral agents; CD8 antigen; Cell activation; COVID-19; Infections; Lymphocytes T; Macrophages; Morbidity; Severe acute respiratory syndrome coronavirus 2; Transgenic mice
• DOI: 10.1101/2022.11.09.515832

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 an 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 signature persist in the lungs of N. brasiliensis exposed mice after clearance of the parasite and establish a primed environment for increased antigen presentation. 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 anti-viral CD8+ T cell responses.Competing Interest StatementThe authors have declared no competing interest.