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Immune Antibodies and Helminth Products Drive CXCR2-Dependent Macrophage-Myofibroblast Crosstalk to Promote Intestinal Repair


To complete their lifecycles, helminth parasites have to migrate through tissues such as the skin, lung, liver and intestine. This migration causes severe tissue damage, resulting in the need for rapid repair to restore the integrity and function of damaged tissues. Protective type 2 immune responses against helminths can repair acute lung damage, but they can also promote liver fibrosis. However, how protective immune mechanisms might contribute to wound healing during enteric nematode infection has remained unclear. Here we show that during a protective antibody response, where helminth larvae are trapped in the intestinal mucosa, macrophages and myofibroblasts secrete chemokines, which promote the repair of helminth-caused lesions. Chemokine secretion by macrophages was triggered by antibodies and helminth products, whilst myofibroblasts produced chemokines directly in response to innate recognition of helminth products. The same chemokines that instructed intestinal repair in mice were also secreted by human macrophages, when co-cultured with immune serum and helminths. Finally, human myofibroblasts closed in vitro scratch wounds more rapidly, when stimulated with the chemokine secretions of helminth-antibody activated human macrophages. Thus, our findings reveal a novel mechanism, by which a protective antibody response can promote the repair of intestinal injury during helminth infection.


Vyšlo v časopise: Immune Antibodies and Helminth Products Drive CXCR2-Dependent Macrophage-Myofibroblast Crosstalk to Promote Intestinal Repair. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004778
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004778

Souhrn

To complete their lifecycles, helminth parasites have to migrate through tissues such as the skin, lung, liver and intestine. This migration causes severe tissue damage, resulting in the need for rapid repair to restore the integrity and function of damaged tissues. Protective type 2 immune responses against helminths can repair acute lung damage, but they can also promote liver fibrosis. However, how protective immune mechanisms might contribute to wound healing during enteric nematode infection has remained unclear. Here we show that during a protective antibody response, where helminth larvae are trapped in the intestinal mucosa, macrophages and myofibroblasts secrete chemokines, which promote the repair of helminth-caused lesions. Chemokine secretion by macrophages was triggered by antibodies and helminth products, whilst myofibroblasts produced chemokines directly in response to innate recognition of helminth products. The same chemokines that instructed intestinal repair in mice were also secreted by human macrophages, when co-cultured with immune serum and helminths. Finally, human myofibroblasts closed in vitro scratch wounds more rapidly, when stimulated with the chemokine secretions of helminth-antibody activated human macrophages. Thus, our findings reveal a novel mechanism, by which a protective antibody response can promote the repair of intestinal injury during helminth infection.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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