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Esser-von Bieren, J. ; Volpe, B.* ; Sutherland, D.B.* ; Bürgi, J.* ; Verbeek, J.S.* ; Marsland, B.J.* ; Urban, J.F.* ; Harris, N.L.*

Immune antibodies and helminth products drive CXCR2-dependent macrophage-myofibroblast crosstalk to promote intestinal repair.

PLoS Pathog. 11:e1004778 (2015)
Publ. Version/Full Text DOI PMC
Open Access Gold
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Helminth parasites can cause considerable damage when migrating through host tissues, thus making rapid tissue repair imperative to prevent bleeding and bacterial dissemination particularly during enteric infection. However, how protective type 2 responses targeted against these tissue-disruptive multicellular parasites might contribute to homeostatic wound healing in the intestine has remained unclear. Here, we observed that mice lacking antibodies (Aid-/-) or activating Fc receptors (Fcrg-/-) displayed impaired intestinal repair following infection with the murine helminth Heligmosomoides polygyrus bakeri (Hpb), whilst transfer of immune serum could partially restore chemokine production and rescue wound healing in Aid-/- mice. Impaired healing was associated with a reduced expression of CXCR2 ligands (CXCL2/3) by macrophages (MΦ) and myofibroblasts (MF) within intestinal lesions. Whilst antibodies and helminths together triggered CXCL2 production by MΦ in vitro via surface FcR engagement, chemokine secretion by intestinal MF was elicited by helminths directly via Fcrg-chain/dectin2 signaling. Blockade of CXCR2 during Hpb challenge infection reproduced the delayed wound repair observed in helminth infected Aid-/- and Fcrg-/- mice. Finally, conditioned media from human MΦ stimulated with infective larvae of the helminth Ascaris suum together with immune serum, promoted CXCR2-dependent scratch wound closure by human MF in vitro. Collectively our findings suggest that helminths and antibodies instruct a chemokine driven MΦ-MF crosstalk to promote intestinal repair, a capacity that may be harnessed in clinical settings of impaired wound healing.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Protective Immunity; Dendritic Cells; Responses; Mice; Receptor; Cxcr2; Activation; Expression; Innate; Inflammation
ISSN (print) / ISBN 1553-7366
e-ISSN 1553-7374
Journal PLoS Pathogens
Quellenangaben Volume: 11, Issue: 3, Pages: , Article Number: e1004778 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place San Francisco
Non-patent literature Publications
Reviewing status Peer reviewed