Macrophage regulation & function in helminth infection

Abstract

Macrophages are innate immune cells with essential roles in host defense, inflammation, immune regulation and repair. During infection with multicellular helminth parasites, macrophages contribute to pathogen trapping and killing as well as to tissue repair and the resolution of type 2 inflammation. Macrophages produce a broad repertoire of effector molecules, including enzymes, cytokines, chemokines and growth factors that govern anti-helminth immunity and repair of parasite-induced tissue damage. Helminth infection and the associated type 2 immune response induces an alternatively activated macrophage (AAM) phenotype that - beyond driving host defense - prevents aberrant Th2 cell activation and type 2 immunopathology. The immune regulatory potential of macrophages is exploited by helminth parasites that induce the production of anti-inflammatory mediators such as interleukin 10 or prostaglandin E₂ to evade host immunity. Here, we summarize current insights into the mechanisms of macrophage-mediated host defense and repair during helminth infection and highlight recent progress on the immune regulatory crosstalk between macrophages and helminth parasites. We also point out important remaining questions such as the translation of findings from murine models to human settings of helminth infection as well as long-term consequences of helminth-induced macrophage reprogramming for subsequent host immunity.

Keywords: Alternatively activated macrophages; Helminth infection; Immune regulation; Immunometabolism; Inflammation; Tissue repair; Type 2 immunity.