Group 2 Innate Lymphoid Cells Are Detrimental to the Control of Infection with Francisella tularensis

Joshua Dow, Urszula M Cytlak, Joshua Casulli, Craig P McEntee, Catherine Smedley, Suzanne H Hodge, Riccardo V D'Elia, Matthew R Hepworth, Mark A Travis

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)618-627
Number of pages10
JournalJournal of immunology (Baltimore, Md. : 1950)
Issue number5
Early online date16 Jan 2023
Publication statusPublished - 1 Mar 2023


  • Animals
  • Mice
  • Francisella tularensis
  • Immunity, Innate
  • Lymphocytes
  • Interleukin-5
  • Cytokines


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