Supplementary Material for: Eosinophils are an endogenous source of IL-4 during filarial infections and contribute to the development of an optimal T helper 2 response

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. Our research uncovers eosinophils as a major source of IL-4, especially during the early phase of filarial infection. Using dblGATA mice lacking eosinophil and subsequently eosinophil-derived IL-4, we reveal their profound impact on the Th2 response. Lack of eosinophils impact Th2 polarization and resulted in impaired type 2 cytokine production. Surprisingly, eosinophil deficiency had no impact on macrophage polarization and proliferation as well as on antibody production. These findings shed new light on IL-4 dynamics and eosinophil effector functions in filarial infections.

白细胞介素-4（Interleukin-4, IL-4）是2型免疫的核心调控因子，在抵御蠕虫等多细胞寄生虫的宿主防御过程中发挥关键作用。本研究以人类丝虫病感染的模型——西门氏丝虫（Litomosoides sigmodontis）感染——为研究对象，聚焦IL-4在此过程中的功能及其细胞来源。我们的研究发现，嗜酸性粒细胞是IL-4的主要产生来源，尤其在丝虫感染早期阶段。通过使用缺失嗜酸性粒细胞及其后续的嗜酸性粒细胞来源IL-4的dblGATA小鼠，我们阐明了其对2型辅助T细胞（Th2）应答的显著调控作用。嗜酸性粒细胞缺失会损害Th2极化过程，并导致2型细胞因子产生能力受损。令人意外的是，嗜酸性粒细胞缺失对巨噬细胞的极化与增殖以及抗体生成均无显著影响。上述研究结果为丝虫感染过程中IL-4的动态变化及嗜酸性粒细胞的效应功能提供了全新的认知视角。