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

• Published in: Journal of innate immunity 2024-01, Vol.16 (1), p.159-172
• Main Authors: Guth, Cécile, Schumacher, Pia Philippa, Vijayakumar, Archena, Borgmann, Hannah, Balles, Helene, Koschel, Marianne, Risch, Frederic, Lenz, Benjamin, Hoerauf, Achim, Hübner, Marc P., Ajendra, Jesuthas
• Format: Article
• Language: English
• Subjects: cd4+ t cells; eosinophils; interleukin-4; macrophages; nematode infection; Research Article
• ISSN: 1662-811X; 1662-8128
• DOI: 10.1159/000536357

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 Plain Language SummaryFilarial nematodes can cause severe diseases like onchocerciasis and lymphatic filariasis, posing a significant public health challenge in tropical regions, putting over a billion people at risk. The WHO categorizes these infections as neglected tropical diseases and aims to eliminate onchocerciasis transmission and lymphatic filariasis as a public health issue by 2030. Filarial nematodes modulate the immune system of their host, and the induction of protective immune responses still requires a better understanding. Eosinophils have been identified as a key immune cell type in the well-established murine model for filarial infection, Litomosoides sigmodontis. However, their precise roles and interactions with other components of the type 2 immune response remain unclear. Our study reveals that eosinophils play a crucial role as a primary source of interleukin-4, the central cytokine in type 2 immunity. By using dblGATA mice, we found that the absence of eosinophils resulted in a reduced T helper 2 response but did not impact the alternative activation of macrophages or antibody production. In summary, our research uncovers an underappreciated function of eosinophils and their significant influence on type 2 immune responses.