A novel regulatory macrophage induced by a helminth molecule instructs IL-10 in CD4(+) T cells and protects against mucosal inflammation

Item Type:	Article
Title:	A novel regulatory macrophage induced by a helminth molecule instructs IL-10 in CD4(+) T cells and protects against mucosal inflammation
Creators Name:	Ziegler, T. and Rausch, S. and Steinfelder, S. and Klotz, C. and Hepworth, M.R. and Kühl, A.A. and Burda, P.C. and Lucius, R. and Hartmann, S.
Abstract:	Immunomodulation is a common feature of chronic helminth infections and mainly attributed to the secretion of bioactive molecules, which target and modify host immune cells. In this study, we show that the helminth immunomodulator AvCystatin, a cysteine protease inhibitor, induces a novel regulatory macrophage (Mreg; AvCystatin-Mreg), which is sufficient to mitigate major parameters of allergic airway inflammation and colitis in mice. A single adoptive transfer of AvCystatin-Mreg before allergen challenge suppressed allergen-specific IgE levels, the influx of eosinophils into the airways, local and systemic Th2 cytokine levels, and mucus production in lung bronchioles of mice, whereas increasing local and systemic IL-10 production by CD4(+) T cells. Moreover, a single administration of AvCystatin-Mreg during experimentally induced colitis strikingly reduced intestinal pathology. Phenotyping of AvCystatin-Mreg revealed increased expression of a distinct group of genes including LIGHT, sphingosine kinase 1, CCL1, arginase-1, and costimulatory molecules, CD16/32, ICAM-1, as well as PD-L1 and PD-L2. In cocultures with dendritic cells and CD4(+) T cells, AvCystatin-Mreg strongly induced the production of IL-10 in a cell-contact-independent manner. Collectively, our data identify a specific suppressive macrophage population induced by a single parasite immunomodulator, which protects against mucosal inflammation.
Keywords:	Acanthocheilonema, Adoptive Transfer, Animal Disease Models, CD4-Positive T-Lymphocytes, Colitis, Helminth Antigens, Immunosuppressive Agents, Inbred BALB C Mice, Inbred C57BL Mice, Inflammation, Interleukin-10, Macrophages, Mucosal Immunity, Pneumonia, Animals, Mice
Source:	Journal of Immunology
ISSN:	0022-1767
Publisher:	American Association of Immunologists
Volume:	194
Number:	4
Page Range:	1555-1564
Date:	15 February 2015
Official Publication:	https://doi.org/10.4049/jimmunol.1401217
PubMed:	View item in PubMed

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