Basophils and Eosinophils in Nematode Infections

Abstract

Helminths remain one of the most prolific pathogens in the world. Following infection helminths interact with various epithelial cell surfaces, including skin, lung, and gut. Recent works have shown that epithelial cells produce a series of cytokines such as TSLP, IL-33, and IL-25 that lead to the induction of innate and acquired type 2 immune responses, which we named Type 2 epithelial cytokines. Although basophils and eosinophils are relatively rare granulocytes under normal conditions (0.5% and 5% in peripheral blood, respectively), both are found with increased frequency in type 2 immunity, including allergy and helminth infections. Recent reports showed that basophils and eosinophils not only express effector functions in type 2 immune reactions, but also manipulate the response toward helminths. Furthermore, basophils and eosinophils play non-redundant roles in distinct responses against various nematodes, providing the potential to intervene at different stages of nematode infection. These findings would be helpful to establish vaccination or therapeutic drugs against nematode infections.

Keywords: type 2 immunity; Th2; Type 2 epithelial cytokines; allergy; basophil; eosinophil; helminth; nematode.

Figure 1

Immune responses against Nippostrongylus brasiliensis (Nb) infection in the skin. Nb leaves the skin and enters the blood and lymphatic vessels within 20 minutes of primary infection. In IL-5 transgenic mice, eosinophils are activated by overexpression of IL-5, and produce the anti-helminthic enzyme, major basic protein (MBP), causing Nb parasites to arrest in the skin lesion during primary infection. However, Nb antigens activate basophils during secondary infection, and correspondingly activate monocytes/macrophages to promote M2-type macrophage differentiation. Activated M2-type macrophages then secrete the anti-nematode enzyme, Arginase-I. Eosinophils are also accumulated in the skin, but the role of these accumulated eosinophils is not yet known. Depletion of basophils allows for Nb parasites to leave the skin, but eosinophils still infiltrate the tissue during secondary infection.

Figure 2

Immune responses against Nippostrongylus brasiliensis (Nb) infection in the lungs. During a primary Nb infection, Nb leaves the lungs before the peak of infiltration of eosinophils and M2-type macrophages to the site of lung infection (68). On the other hand, during re-infection of Nb, activated Innate Lymphoid Cell 2 cells (ILC2s) and CXCR6⁺ST2⁺ memory Th2 cells produce IL-5 and IL-13. IL-5 and IL-13 promote lung infiltration, activation and major basic protein (MBP) production by eosinophils. In addition, M2-type macrophages are also induced by type 2 cytokines that could be produced by ILC2s, Th2 cells and/or neutrophils in re-infection.