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) |
|---|---|
| Journal | Mucosal Immunology |
| DOIs | |
| State | Accepted/In press - Jan 1 2020 |
Fingerprint
PubMed: MeSH publication types
- Journal Article
Cite this
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 journal › Article
}
TY - JOUR
T1 - Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance
AU - Dobson, Hannah E.
AU - Dias, Lucas Dos Santos
AU - Kohn, Elaine M.
AU - Fites, Scott
AU - Wiesner, Darin L.
AU - Dileepan, Thamotharampillai
AU - Kujoth, Gregory C.
AU - Abraham, Ambily
AU - Ostroff, Gary R.
AU - Klein, Bruce S.
AU - Wüthrich, Marcel
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85077474865&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077474865&partnerID=8YFLogxK
U2 - 10.1038/s41385-019-0244-3
DO - 10.1038/s41385-019-0244-3
M3 - Article
C2 - 31900406
AN - SCOPUS:85077474865
JO - Mucosal Immunology
JF - Mucosal Immunology
SN - 1933-0219
ER -