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Extracts of the tapeworm, Hymenolepis diminuta, recruit CCR2 + PDL1 + Myeloid Cells with the capacity to inhibit dextran sodium sulphate induced‐colitis
Author(s) -
Lopes Fernando,
Reyes Jose Luiz,
Leung Gabriella,
Mancini Nicole,
Wang Arthur,
McKay Derek
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.57.1
Subject(s) - colitis , adoptive cell transfer , immunology , hymenolepis diminuta , chemistry , t cell , microbiology and biotechnology , medicine , biology , immune system , helminths , cestoda
Background Awareness of the immunological basis of host‐parasite interactions can reveal new approaches to cure and/or treat inflammatory disease. We have shown that mice infected with the tapeworm Hymenolepis diminuta (Hd) or systemic delivery of worm antigen (HdAg) developed significantly less severe dinitrobenzene sulphonic acid (DNBS)‐induced murine colitis. Aim In ongoing analyses of this helminth‐mouse model system we assessed the effect of systemic delivery of HdAg and adoptive transfer of HdAg‐recruited peritoneal exudate cells (PECs) on the outcome of dextran sodium sulphate (DSS)‐induced colitis. Methods Colitis was induced by 5 days of DSS in drinking water and 3 days of normal water in wild‐type (WT) mice ± HdAg or adoptive transfer of HdAg‐recruited total PECs or F4/80 + Ly6G lo sorted cells. Disease was assessed by colon length, weight loss, a cumulative disease activity score and histopathology. Cytokine levels were assessed by ELISA. T cell proliferation was assessed in anti‐CD3+ anti‐CD28‐treated splenic CD4 + T cells co‐cultured with PECs recruited by PBS or HdAg. Results HdAg suppressed DSS colitis reducing splenic IFNγ, IL‐17 and TNF α and increasing IL‐10 production. Treatment with HdAg resulted in a CCR2‐dependent recruitment of F4/80 + Ly6G lo monocytic‐like myeloid‐derived suppressor cells (MDSCs) into the peritoneum. Adoptive transfer of these cells blocked DSS‐colitis. The mixed peritoneal cells recruited in response to HdAg, blocked anti‐CD3+anti‐CD28 antibody evoked T cell proliferation via nitric oxide. Conclusion Injection of an extract of adult H. diminuta inhibits DSS‐induced colitis and was accompanied by recruitment of immunosuppressive CCR2 + PDL1 + monocytic‐type MDSCs. The adoptive transfer of the HdAg‐evoked MDSCs inhibits DSS‐induced colitis, demonstrating a novel aspect by which helminth‐derived molecules could suppress intestinal inflammation. Support or Funding Information CIHR NSERC CREATE, Host‐Parasite Interactions Program