Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance

Hannah E. Dobson, Lucas Dos Santos Dias, Elaine M. Kohn, Scott Fites, Darin L. Wiesner, Thamotharampillai Dileepan, Gregory C. Kujoth, Ambily Abraham, Gary R. Ostroff, Bruce S. Klein, Marcel Wüthrich

Research output: Contribution to journalArticle

Abstract

Priming at the site of natural infection typically elicits a protective T cell response against subsequent pathogen encounter. Here, we report the identification of a novel fungal antigen that we harnessed for mucosal vaccination and tetramer generation to test whether we can elicit protective, antigen-specific tissue-resident memory (Trm) CD4+ T cells in the lung parenchyma. In contrast to expectations, CD69+, CXCR3+, CD103 Trm cells failed to protect against a lethal pulmonary fungal infection. Surprisingly, systemic vaccination induced a population of tetramer+ CD4+ T cells enriched within the pulmonary vasculature, and expressing CXCR3 and CX3CR1, that migrated to the lung tissue upon challenge and efficiently protected mice against infection. Mucosal vaccine priming of Trm may not reliably protect against mucosal pathogens.

Original languageEnglish (US)
JournalMucosal Immunology
DOIs
StateAccepted/In press - Jan 1 2020

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Antigens
T-Lymphocytes
Lung
Fungal Lung Diseases
Vaccination
Fungal Antigens
Infection
Vaccines
Population

PubMed: MeSH publication types

  • Journal Article

Cite this

Dobson, H. E., Dias, L. D. S., Kohn, E. M., Fites, S., Wiesner, D. L., Dileepan, T., ... Wüthrich, M. (Accepted/In press). Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance. Mucosal Immunology. https://doi.org/10.1038/s41385-019-0244-3

Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance. / Dobson, Hannah E.; Dias, Lucas Dos Santos; Kohn, Elaine M.; Fites, Scott; Wiesner, Darin L.; Dileepan, Thamotharampillai; Kujoth, Gregory C.; Abraham, Ambily; Ostroff, Gary R.; Klein, Bruce S.; Wüthrich, Marcel.

In: Mucosal Immunology, 01.01.2020.

Research output: Contribution to journalArticle

Dobson, HE, Dias, LDS, Kohn, EM, Fites, S, Wiesner, DL, Dileepan, T, Kujoth, GC, Abraham, A, Ostroff, GR, Klein, BS & Wüthrich, M 2020, 'Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance', Mucosal Immunology. https://doi.org/10.1038/s41385-019-0244-3
Dobson, Hannah E. ; Dias, Lucas Dos Santos ; Kohn, Elaine M. ; Fites, Scott ; Wiesner, Darin L. ; Dileepan, Thamotharampillai ; Kujoth, Gregory C. ; Abraham, Ambily ; Ostroff, Gary R. ; Klein, Bruce S. ; Wüthrich, Marcel. / Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance. In: Mucosal Immunology. 2020.
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