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Title: Innate immunological function of TH2 cells in vivo

item GUO, LIYING - National Instiute Of Allergy And Infectious Diseases (NIAID, NIH)
item HUANG, YUEFENG - National Instiute Of Allergy And Infectious Diseases (NIAID, NIH)
item CHEN, XI - National Instiute Of Allergy And Infectious Diseases (NIAID, NIH)
item HU-LI, JANE - National Instiute Of Allergy And Infectious Diseases (NIAID, NIH)
item Urban, Joseph
item PAUL, WILLIAM - National Instiute Of Allergy And Infectious Diseases (NIAID, NIH)

Submitted to: Nature Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/31/2015
Publication Date: 10/1/2015
Citation: Guo, L., Huang, Y., Chen, X., Hu-Li, J., Urban Jr, J.F., Paul, W.E. 2015. Innate immunological function of TH2 cells in vivo. Nature Immunology. 16:1051-1059.

Interpretive Summary: Helminth (worm) infections are a global health concern in humans as well as livestock because they establish chronic and repeated infections. Anthelmintic therapy (anti-parasite drug treatment) has been the most effective strategy to control worm infection but the development of parasite drug resistance has required alternative strategies and energized more traditional approaches for control that include immune system activation. The recent characterization of immune cells that are part of the innate immune response, i.e. those that are activated in a naive host that has not previously been infected, has stimulated interest in the role of innate cells in acquired immunity to worm parasites. This study characterized the relative contribution of a population of cells called innate lymphoid cell 2 (ILC2) that do not have specific receptors for parasite products (antigens) but respond in a fashion similar to acquired immune cells that do specifically respond to antigens. The ILC2 expand during infection with worm parasites and contribute to a more vigorous response to distantly related parasites but also to active plant proteins like papain and allergens from house dust mites. The advantage of this contribution is that humans and animals that are exposed to a variety of different types of parasites respond more vigorously to broadly eliminate the infections. The danger, however, is that the responses can be intense and cause overt disease in tissues like the lung that are exposed to these potent products. Understanding how the ILC is activated and expanded can also provide information on how to limit the intensity of the response to not express harmful reactions to common allergens and infections. This information will be of interest to scientists interested in developing useful and safe procedures to protect humans and livestock from parasitic infection and allergic disease.

Technical Abstract: Th2 cells produce IL-13 when stimulated by papain or house dust mites (HDM) and induce eosinophilic inflammation. This innate response of cells of the adaptive immune system is dependent on IL-33-, not T cell receptor-, based stimulation. While type 2 innate lymphoid cells (ILC2s) are the dominant innate producers of IL-13 in naïve animals, we show here that in helminth-infected mice, Th2 cells expand strikingly in number and become major mediators of innate type II responses. They make important contributions to HDM-induced antigen-non-specific eosinophilic inflammation and to protecting mice recovering from infection with Ascaris suum against subsequent infection with the phylogenetically distant nematode Nippostrongylus brasiliensis. Our findings reveal a previously unappreciated role of effector Th2 cells during innate immune responses.