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

J Innate Immun. 2024;16(1):159-172. doi: 10.1159/000536357. Epub 2024 Feb 26.

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.

Keywords: CD4+ T cells; Eosinophils; Interleukin-4; Macrophages; Nematode infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Disease Models, Animal
  • Eosinophils* / immunology
  • Female
  • Filariasis* / immunology
  • Filarioidea* / immunology
  • Interleukin-4* / immunology
  • Interleukin-4* / metabolism
  • Macrophages / immunology
  • Mice
  • Mice, Inbred BALB C
  • Th2 Cells* / immunology

Substances

  • Il4 protein, mouse
  • Interleukin-4

Grants and funding

A.H. and M.H. were funded under Germany’s Excellence Strategy – EXC2151-390873048, and are members of the German Center for Infection Research (DZIF). M.H. received funding from the German Center for Infection Research (TTU 09.701).