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

Ziegler, Thomas; Rausch, Sebastian; Steinfelder, Svenja; Klotz, Christian; Hepworth, Matthew R; Kühl, Anja A; Burda, Paul-Christian; Lucius, Richard; Hartmann, Susanne (2015). A novel regulatory macrophage induced by a helminth molecule instructs IL-10 in CD4+ T cells and protects against mucosal inflammation. Journal of immunology, 194(4), pp. 1555-1564. American Association of Immunologists 10.4049/jimmunol.1401217

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Burda, Paul-Christian

Subjects:

500 Science > 570 Life sciences; biology
500 Science

ISSN:

0022-1767

Publisher:

American Association of Immunologists

Language:

English

Submitter:

Volker Heussler

Date Deposited:

20 Aug 2015 10:41

Last Modified:

20 Aug 2015 10:41

Publisher DOI:

10.4049/jimmunol.1401217

PubMed ID:

25589067

BORIS DOI:

10.7892/boris.71022

URI:

https://boris.unibe.ch/id/eprint/71022

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