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Type 2 innate immunity in Helminth infection is induced redundantly and acts autonomously following CD11c+ cell depletion

Smith, Katherine, Harcus, Y., Garbi, N., Hammerling, G. J., MacDonald, A. S. and Maizels, R. M. 2012. Type 2 innate immunity in Helminth infection is induced redundantly and acts autonomously following CD11c+ cell depletion. Infection and Immunity 80 (10) , pp. 3481-3489. 10.1128/IAI.00436-12

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Infection with gastrointestinal helminths generates a dominant type 2 response among both adaptive (Th2) and innate (macrophage, eosinophil, and innate lymphoid) immune cell types. Two additional innate cell types, CD11chigh 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 first confirmed the requirement for DCs in stimulating Th2 adaptive immunity against these helminths through depletion of CD11chigh cells by administration of diphtheria toxin to CD11c.DOG mice. In contrast, responsiveness was intact in mice depleted of basophils by antibody treatment. Th2 responses can be induced by adoptive transfer of DCs, but not basophils, exposed to soluble excretory-secretory products from these helminths. However, innate type 2 responses arose equally strongly in the presence or absence of CD11chigh 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 CD11chigh cells or basophils. Thus, while CD11chigh DCs initiate helminth-specific adaptive immunity, innate type 2 cells are able to mount an autonomous response to the challenge of parasite infection.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QR Microbiology > QR180 Immunology
Publisher: American Society for Microbiology
ISSN: 0019-9567
Date of Acceptance: 16 July 2012
Last Modified: 18 Jan 2017 05:35

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