Group 2 innate lymphoid cells are detrimental to the control of infection with Francisella tularensis

Dow, Joshua and Cytlak, Urszula M. and Casulli, Joshua and McEntee, Craig P. and Smedley, Catherine and Hodge, Suzanne H. and D'Elia, Riccardo V. and Hepworth, Matthew R. and Travis, Mark A. (2023) Group 2 innate lymphoid cells are detrimental to the control of infection with Francisella tularensis. Journal of Immunology, 210 (5). pp. 618-627. ISSN 0022-1767 (https://doi.org/10.4049/jimmunol.2100651)

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Abstract

Innate lymphoid cells (ILCs) are capable of rapid response to a wide variety of immune challenges, including various respiratory pathogens. Despite this, their role in the immune response against the lethal intracellular bacterium Francisella tularensis is not yet known. In this study, we demonstrate that infection of the airways with F. tularensis results in a significant reduction in lung type 2 ILCs (ILC2s) in mice. Conversely, the expansion of ILC2s via treatment with the cytokine IL-33, or by adoptive transfer of ILC2s, resulted in significantly enhanced bacterial burdens in the lung, liver, and spleen, suggesting that ILC2s may favor severe infection. Indeed, specific reduction of ILC2s in a transgenic mouse model results in a reduction in lung bacterial burden. Using an in vitro culture system, we show that IFN-γ from the live vaccine strain–infected lung reduces ILC2 numbers, suggesting that this cytokine in the lung environment is mechanistically important in reducing ILC2 numbers during infection. Finally, we show Ab-mediated blockade of IL-5, of which ILC2s are a major innate source, reduces bacterial burden postinfection, suggesting that IL-5 production by ILC2s may play a role in limiting protective immunity. Thus, overall, we highlight a negative role for ILC2s in the control of infection with F. tularensis. Our work therefore highlights the role of ILC2s in determining the severity of potentially fatal airway infections and raises the possibility of interventions targeting innate immunity during infection with F. tularensis to benefit the host.

  • Item type:Article
    ID code:83847
    Dates:
    Date
    Event
    1 March 2023
    Published
    4 January 2023
    Published Online
    2 December 2022
    Accepted
    2 July 2021
    Submitted
    Subjects:Medicine > Pharmacy and materia medica > Pharmaceutical chemistry
    Department:UNSPECIFIED
    Depositing user: Pure Administrator
    Date deposited:26 Jan 2023 11:28
    Last modified:18 Apr 2024 08:41
    URI:https://strathprints.strath.ac.uk/id/eprint/83847
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