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

doi:10.1038/s41385-019-0244-3

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

Microbiology

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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 language	English (US)
Pages (from-to)	518-529
Number of pages	12
Journal	Mucosal Immunology
Volume	13
Issue number	3
DOIs	https://doi.org/10.1038/s41385-019-0244-3
State	Published - May 1 2020

Bibliographical note

Funding Information:
This work was supported by National Institute of Health Grant AI093553 (to MW) AI035681 (to BK) and AI040996 (to BK and MW). All flow data were collected at the University of Wisconsin Carbone Center Flow Lab on the BD LSR Fortessa with the NIH Shared Instrumentation Grant 1S100OD018202–01. We thank Drs Marc Jenkins from the Center for Immunology, Department of Microbiology and Immunology at the University of Minnesota for his assistance in generating the tetramer, Suresh Marulasiddappa from the Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison for helpful discussions and Nydiaris Hernandez-Santos from the Department of Pediatrics at the University of Wisconsin for expert technical assistance.

Funding Information:
Generation of data (HED, LDSD, EMK, SF, DLW, TD, GK, AA, GRO): analysis of data and statistical analysis (HED, LDSD, EMK), paper preparation (HED, MW, BSK); specialized equipment and reagent generation (TD, AA, GRO), Study design (MW and BSK), concept and financial support (MW and BSK).

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Journal Article
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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, Vol. 13, No. 3, 01.05.2020, p. 518-529.

Research output: Contribution to journal › Article › peer-review

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 ; Vol. 13, No. 3. pp. 518-529.

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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.",

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

Abstract

Bibliographical note

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