Macrophages treated with antigen from the tapeworm Hymenolepis diminuta condition CD25+ T cells to suppress colitis

FASEB J. 2019 Apr;33(4):5676-5689. doi: 10.1096/fj.201802160R. Epub 2019 Jan 22.


Macrophages play central roles in immunity as early effectors and modulating adaptive immune reponses; we implicated macrophages in the anticolitic effect of infection with the tapeworm Hymenolepis diminuta. Here, gene arrays revealed that H. diminuta antigen (HdAg) evoked a program in murine macrophages distinct from that elicited by IL-4. Further, HdAg suppressed LPS-evoked release of TNF-α and IL-1β from macrophages via autocrine IL-10 signaling. In assessing the ability of macrophages treated in vitro with an extract of H. diminuta [M(HdAg)] to affect disease, intravenous, but not peritoneal, injection of M(HdAg) protected wild-type but not RAG1-/- mice from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Administration of splenic CD4+ T cells from in vitro cocultures with M(HdAg), but not those cocultured with M(IL-4) cells, inhibited DNBS-induced colitis; fractionation of the T-cell population indicated that the CD4+CD25+ T cells from cocultures with M(HdAg) drove the suppression of DNBS-induced colitis. Use of IL-4-/- or IL-10-/- CD4+ T cells revealed that neither cytokine alone from the donor cells was essential for the anticolitic effect. These data illustrate that HdAg evokes a unique regulatory program in macrophages, identifies HdAg-evoked IL-10 suppression of macrophage activation, and reveals the ability of HdAg-treated macrophages to educate ( i.e., condition) and mobilize CD4+CD25+ T cells, which could be deployed to treat colonic inflammation.-Reyes, J. L., Lopes, F., Leung, G., Jayme, T. S., Matisz, C. E., Shute, A., Burkhard, R., Carneiro, M., Workentine, M. L., Wang, A., Petri, B., Beck, P. L., Geuking, M. B., McKay, D. M., Macrophages treated with antigen from the tapeworm Hymenolepis diminuta condition CD25+ T cells to suppress colitis.

Keywords: helminth; inflammatory bowel disease; interleukin-10; intestine; macrophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Helminth / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cestoda / immunology*
  • Colitis / immunology*
  • Colitis / parasitology
  • Colon / immunology
  • Colon / parasitology
  • Cytokines / immunology
  • Humans
  • Hymenolepis diminuta / immunology*
  • Interleukin-10 / immunology
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Interleukin-4 / immunology
  • Macrophage Activation / immunology
  • Macrophages / immunology*
  • Macrophages / parasitology
  • Male
  • Mice
  • Mice, Inbred BALB C


  • Antigens, Helminth
  • Cytokines
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-10
  • Interleukin-4