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

Hilligan, K. L.; Oyesola, O. O.; Namasivayam, S.; Howard, N.; Clancy, C. S.; Oland, S. D.; Garza, N. L.; Lafont, B. A. P.; Johnson, R. F.; Mayer-Barber, K. D.; Sher, A.; Loke, P.

doi:10.1101/2022.11.09.515832

bioRxiv · 10.1101/2022.11.09.515832

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

Hilligan, K. L.·Oyesola, O. O.·Namasivayam, S.·Howard, N.·Clancy, C. S.·Oland, S. D.·Garza, N. L.·Lafont, B. A. P.·Johnson, R. F.·Mayer-Barber, K. D.·Sher, A.·Loke, P.

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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 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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/515832v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@1c17a22org.highwire.dtl.DTLVardef@13967b3org.highwire.dtl.DTLVardef@1c723a7org.highwire.dtl.DTLVardef@f5e038_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Hilligan, K. L., Oyesola, O. O., Namasivayam, S., Howard, N., Clancy, C. S., Oland, S. D., Garza, N. L., Lafont, B. A. P., Johnson, R. F., Mayer-Barber, K. D., Sher, A., Loke, P.. 2022-11-10. Helminth exposure protects against murine SARS-CoV-2 infection through macrophage dependent T cell activation. https://doi.org/10.1101/2022.11.09.515832

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