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

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.

SUBMITTER: Dobson HE

PROVIDER: S-EPMC7183437 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Dobson Hannah E HE Dias Lucas Dos Santos LDS Kohn Elaine M EM Fites Scott S Wiesner Darin L DL Dileepan Thamotharampillai T Kujoth Gregory C GC Abraham Ambily A Ostroff Gary R GR Klein Bruce S BS Wüthrich Marcel M

Mucosal immunology 20200103 3

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 protec ...[more]

PMID: 31900406

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Project description:Migratory birds are an increasing focus of interest when it comes to infection dynamics and the spread of avian influenza viruses (AIV). However, we lack detailed understanding migratory birds' contribution to local AIV prevalence levels and their downstream socio-economic costs and threats.To explain the potential differential roles of migratory and resident birds in local AIV infection dynamics, we used a susceptible-infectious-recovered (SIR) model. We investigated five (mutually non- exclusive) mechanisms potentially driving observed prevalence patterns: 1) a pronounced birth pulse (e.g. the synchronised annual influx of immunologically naïve individuals), 2) short-term immunity, 3) increase of susceptible migrants, 4) differential susceptibility to infection (i.e. transmission rate) for migrants and residents, and 5) replacement of migrants during peak migration.SIR models describing all possible combinations of the five mechanisms were fitted to individual AIV infection data from a detailed longitudinal surveillance study in the partially migratory mallard duck (Anas platyrhynchos). During autumn and winter, the local resident mallard community also held migratory mallards that exhibited distinct AIV infection dynamics.Replacement of migratory birds during peak migration in autumn was found to be the most important mechanism driving the variation in local AIV infection patterns. This suggests that a constant influx of migratory birds, likely immunological naïve to locally circulating AIV strains, is required to predict the observed temporal prevalence patterns and the distinct differences in prevalence between residents and migrants.Synthesis and applications. Our analysis reveals a key mechanism that could explain the amplifying role of migratory birds in local avian influenza virus infection dynamics; the constant flow and replacement of migratory birds during peak migration. Aside from monitoring efforts, in order to achieve adequate disease management and control in wildlife - with knock-on effects for livestock and humans, - we conclude that it is crucial, in future surveillance studies, to record host demographical parameters such as population density, timing of birth and turnover of migrants.

Dataset Information

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

Publications

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

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