Group 2 Innate Lymphoid Cells Are Detrimental to the Control of Infection with Francisella tularensis.
Group 2 Innate Lymphoid Cells Are Detrimental to the Control of Infection with Francisella tularensis.
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DOI：
10.4049/jimmunol.2100651
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发表时间：
2023-03-01
影响因子：
4.4
通讯作者：
Travis, Mark A.
中科院分区：
文献类型：
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作者：
Dow, Joshua;Cytlak, Urszula M.;Casulli, Joshua;McEntee, Craig P.;Smedley, Catherine;Hodge, Suzanne H.;D'Elia, Riccardo, V;Hepworth, Matthew R.;Travis, Mark A.
提高ILC 2数量增加土拉热弗朗西丝菌细菌负荷。减少ILC 2数量促进土拉热弗朗西丝菌细菌清除。IFN-γ减少ILC 2，ILC 2产生IL-5对细菌清除有害。先天性淋巴样细胞（ILC）能够快速响应各种免疫挑战，包括各种呼吸道病原体。尽管如此，它们在针对致命的细胞内细菌土拉弗朗西斯菌的免疫应答中的作用尚不清楚。在这项研究中，我们证明了呼吸道感染F。土拉热导致小鼠中肺2型ILC（ILC 2）的显著减少。相反，通过用细胞因子IL-33处理或通过ILC 2的过继转移来扩增ILC 2导致肺、肝和脾中的细菌负荷显著增加，表明ILC 2可能有利于严重感染。事实上，转基因小鼠模型中ILC 2的特异性减少导致肺细菌负荷的减少。使用体外培养系统，我们表明来自活疫苗株感染的肺的IFN-γ减少ILC 2数量，表明肺环境中的这种细胞因子在感染期间减少ILC 2数量方面具有重要的机制。最后，我们表明抗体介导的IL-5，其中ILC 2是一个主要的先天性来源，封锁，减少感染后的细菌负荷，这表明IL-5的生产ILC 2可能在限制保护性免疫中发挥作用。因此，总的来说，我们强调了ILC 2在控制F感染中的负面作用。土拉热。因此，我们的工作强调了ILC 2在决定潜在致命性气道感染严重程度方面的作用，并提出了在F感染期间针对先天免疫进行干预的可能性。土拉热菌对宿主有益
Enhancing ILC2 numbers increases Francisella tularensis bacterial burden. Reducing ILC2 numbers promotes Francisella tularensis bacterial clearance. IFN-γ reduces ILC2s, with ILC2 production of IL-5 detrimental to bacterial clearance. 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.
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影响因子：
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作者：
Kadel S;Ainsua-Enrich E;Hatipoglu I;Turner S;Singh S;Khan S;Kovats S
通讯作者：
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影响因子：
32.4
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影响因子：
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Locksley RM
影响因子：
7.3
作者：
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通讯作者：
Duerr CU