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

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...

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Published inbioRxiv
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
LanguageEnglish
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
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Summary: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.
DOI:10.1101/2022.11.09.515832