Influenza infection fortifies local lymph nodes to promote lung-resident heterosubtypic immunity

Author:

Paik Daniel H.12ORCID,Farber Donna L.123ORCID

Affiliation:

1. Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY

2. Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY

3. Department of Surgery, Columbia University Medical Center, New York, NY

Abstract

Influenza infection generates tissue-resident memory T cells (TRMs) that are maintained in the lung and can mediate protective immunity to heterologous influenza strains, but the precise mechanisms of local T cell–mediated protection are not well understood. In a murine heterosubtypic influenza challenge model, we demonstrate that protective lung T cell responses derive from both in situ activation of TRMs and the enhanced generation of effector T cells from the local lung draining mediastinal lymph nodes (medLNs). Primary infection fortified the medLNs with an increased number of conventional dendritic cells (cDCs) that mediate enhanced priming of T cells, including those specific for newly encountered epitopes; cDC depletion during the recall response diminished medLN T cell generation and heterosubtypic immunity. Our study shows that during a protective recall response, cDCs in a fortified LN environment enhance the breadth, generation, and tissue migration of effector T cells to augment lung TRM responses.

Funder

National Institutes of Health

CUMC

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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