Memory TH2 cells induce alternatively activated macrophages to mediate protection against nematode parasites

Abstract

Although primary and memory responses against bacteria and viruses have been studied extensively, T helper type 2 (T_H2) effector mechanisms leading to host protection against helminthic parasites remain elusive¹. Examination of the intestinal epithelial submucosa of mice after primary and secondary infections by a natural gastrointestinal parasite revealed a distinct immune-cell infiltrate after challenge, featuring interleukin-4–expressing memory CD4⁺ T cells that induced IL-4 receptor^hi (IL-4R^hi) CD206⁺ alternatively activated macrophages². In turn, these alternatively activated macrophages (AAMacs) functioned as important effector cells of the protective memory response contributing to parasite elimination, demonstrating a previously unknown mechanism for host protection against intestinal helminths.