Innate type 2 immunity in helminth infection is induced redundantly and acts autonomously following CD11c+ cell depletion

Katherine A Smith, Yvonne Harcus, Natalio Garbi, Günter J Hämmerling, Andrew S Macdonald, Rick M Maizels

Research output: Contribution to journalArticlepeer-review


Infection with gastrointestinal helminths generates a dominant type-2 response amongst both adaptive (Th2) and innate (macrophage, eosinophil and innate lymphoid) immune cell types. Two additional innate cell types, CD11c(high) dendritic cells (DCs) and basophils, have been implicated in the genesis of type 2 immunity. Investigating the type 2 response to intestinal nematode parasites, including Heligmosomoides polygyrus and Nippostrongylus brasiliensis, we show first that Th2 responses can be induced by adoptive transfer of DCs, but not basophils, exposed to soluble excretory-secretory products from these helminths. The requirement for DCs in stimulating Th2 adaptive immunity against these helminths was further confirmed through depletion of CD11c(high) cells by administration of diphtheria toxin to CD11c.DOG mice. In contrast, responsiveness was intact in mice depleted of basophils by antibody treatment. However, innate type 2 responses arose equally strongly in the presence or absence of CD11c(high) cells or basophils; thus, in CD11c.DOG mice, the alternative activation of macrophages, as measured by expression of Arginase-1, RELM-α and Ym-1 (Chi3L3) in the intestine following H. polygyrus infection, or in the lung following N. brasiliensis infection, was unaltered by depletion of CD11c-expressing DCs and alveolar macrophages, or by antibody-mediated basophil depletion. Similarly, goblet cell-associated RELM-β in lung and intestinal tissues, lung eosinophilia and expansion of innate lymphoid ("nuocyte") populations all proceeded irrespective of depletion of CD11c(high) cells or basophils. Thus, while CD11c(high) DCs initiate helminth-specific adaptive immunity, innate type 2 cells are able to mount an autonomous response to the challenge of parasite infection.
Original languageEnglish
Pages (from-to)3481-3489
JournalInfection and Immunity
Issue number10
Publication statusPublished - 2012


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