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Title: Immune antibodies and helminth products promote CXCR2-dependent repair of parasite-induced injury

item VON BIEREN, JULIA - Ecole Polytechnique Federale De Lausanne (EPFL)
item VOLPE, BEATRICE - Ecole Polytechnique Federale De Lausanne (EPFL)
item SUTHERLAND, DUNCAN - Ecole Polytechnique Federale De Lausanne (EPFL)
item BURGI, JEROME - Ecole Polytechnique Federale De Lausanne (EPFL)
item VERBEEK, SJEF - Leiden University Medical Center
item MARSLAND, BENJAMIN - University Of Lausanne
item Urban, Joseph
item HARRIS, NICOLA - Ecole Polytechnique Federale De Lausanne (EPFL)

Submitted to: PLoS Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/3/2015
Publication Date: 3/25/2015
Publication URL: http://doi:10.1371/journal.ppat.1004778
Citation: Von Bieren, J.E., Volpe, B., Sutherland, D.B., Burgi, J., Verbeek, S., Marsland, B.J., Urban Jr, J.F., Harris, N.L. 2015. Immune antibodies and helminth products promote CXCR2-dependent repair of parasite-induced injury. PLoS Pathogens. 11(3):e1004778.

Interpretive Summary: Helminth (worm) infections are a global health concern because they establish chronic and repeated infections, but they also have potent immune-modulating activities that include anti-inflammatory responses and the capacity to induce tissue repair. The effector mechanisms that promote repair of host tissues following parasitic worm migration are not well characterized. Previous work identified the interaction between the worm and antibody that activates host cells called macrophages to produce products that limit tissue disruption. The current work shows that two specific proteins are released by macrophages in the presence of worm products and host antibodies that bind those worm products. In the absence of host antibody binding to cell receptors, the wound caused by worm migration is not properly closed leading to greater tissue destruction. Of further interest was the observation that these celluar products released by worm products and antibody were also useful for artificially induced wound healing in culture indicating a more general role in tissue repair of wounds unrelated to parasite migration. These results could lead to processing of worm products that could improve wound healing.

Technical Abstract: Helminth parasites cause massive damage when migrating through host tissues, thus making rapid tissue repair imperative to prevent bleeding and bacterial dissemination. We observed that mice lacking antibodies (AID-/-) or activating Fc receptors (FcR'-/-) displayed impaired intestinal repair following infection with the murine helminth Heligmosomoides polygyrus. Impaired healing was associated with a reduced expression of CXCR2 ligands by macrophages (MF) and myofibroblasts (MF) within intestinal lesions. Whilst chemokine production by MF was triggered by helminth-antibody complexes in an FcR-dependent fashion, secretion by MF was elicited directly by helminth products via FcR'-chain/dectin-2 signaling. Blockade of CXCR2 reproduced the delayed wound repair observed in helminth infected AID-/- and FcR'-/- mice. Finally, conditioned medium from human macrophages stimulated with Ascaris suum or Schistosoma mansoni products, together with immune serum, promoted CXCR2-dependent wound closure by human MF. Collectively our findings suggest that immune antibodies promote wound repair following the migration of helminth larvae through host tissues.