Eosinophils in Helminth Infection: Defenders and Dupes

Abstract

Eosinophilia is a central feature of the host response to helminth infection. Larval stages of parasitic worms are killed in vitro by eosinophils in the presence of specific antibodies or complement. These findings established host defense as the paradigm for eosinophil function. Recently, studies in eosinophil-ablated mouse strains have revealed an expanded repertoire of immunoregulatory functions for this cell. Other reports document crucial roles for eosinophils in tissue homeostasis and metabolism, processes that are central to the establishment and maintenance of parasitic worms in their hosts. In this review, we summarize current understanding of the significance of eosinophils at the host-parasite interface, highlighting their distinct functions during primary and secondary exposure.

Keywords: eosinophil; helminth; type 2 immunity.

Figure 1. Model of eosinophil mediated influences on primary and secondary infection by Trichinella spiralis

In primary infection, Trichinella induces a mixed Th1 and Th2 immune response associated with eosinophilia in skeletal muscle. By secreting IL-10, eosinophils promote the expansion of IL-10-producing myeloid dendritic cells (DCs), and enhance the production of IL-10 by CD4⁺CD25⁻ T cells. In macrophages and neutrophils, the production of nitric oxide (NO) by interferon-γ (IFN-γ)-activated inducible nitric oxide synthase (iNOS) is suppressed by IL-10, thereby promoting survival of muscle larvae. Independent of the adaptive immune response, eosinophils and IL-4 promote larval growth by controlling activation of STAT1, a signaling molecule that is known to attenuate insulin sensitivity and impair glucose uptake. The identity of cell(s) responsible for STAT1-dependent gene expression is not known. In secondary infection, eosinophils cooperate with antibodies to interfere with migratory newborn larvae (NBL), preventing their colonization of skeletal muscle and completion of the life-cycle.

Figure 2. Life cycles of selected helminths

Different phases of infection in the mammalian host are highlighted in red. Symbols indicate life stages impacted by eosinophils in primary (|) or secondary (#) infection.