Eosinophils Are an Endogenous Source of Interleukin-4 during Filarial Infections and Contribute to the Development of an Optimal T Helper 2 Response

Cecile Guth, Pia Philippa Schumacher, Archena Vijayakumar, Hannah Borgmann, Helene Balles,Marianne Koschel,Frederic Risch,Benjamin Lenz,Achim Hoerauf, Marc P. Huebner,Jesuthas Ajendra

JOURNAL OF INNATE IMMUNITY(2024)

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Abstract
Introduction: Interleukin-4 (IL-4) is a central regulator of type 2 immunity, crucial for the defense against multicellular parasites like helminths. This study focuses on its roles and cellular sources during Litomosoides sigmodontis infection, a model for human filarial infections. Methods: Utilizing an IL-4 secretion assay, investigation into the sources of IL-4 during the progression of L. sigmodontis infection was conducted. The impact of eosinophils on the Th2 response was investigated through experiments involving dblGATA mice, which lack eosinophils and, consequently, eosinophil-derived IL-4. Results: The absence of eosinophils notably influenced Th2 polarization, leading to impaired production of type 2 cytokines. Interestingly, despite this eosinophil deficiency, macrophage polarization, proliferation, and antibody production remained unaffected. Conclusion: Our research uncovers eosinophils as a major source of IL-4, especially during the early phase of filarial infection. Consequently, these findings shed new light on IL-4 dynamics and eosinophil effector functions in filarial infections
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Key words
Eosinophils,Interleukin-4,Nematode infection,CD4(+) T cells,Macrophages
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