Hookworm excretory/secretory products induce interleukin-4 (IL-4)+ IL-10+ CD4+ T cell responses and suppress pathology in a mouse model of colitis

Infect Immun. 2013 Jun;81(6):2104-11. doi: 10.1128/IAI.00563-12. Epub 2013 Apr 1.


Evidence from human studies and mouse models shows that infection with parasitic helminths has a suppressive effect on the pathogenesis of some inflammatory diseases. Recently, we and others have shown that some of the suppressive effects of hookworms reside in their excretory/secretory (ES) products. Here, we demonstrate that ES products of the hookworm Ancylostoma caninum (AcES) suppress intestinal pathology in a model of chemically induced colitis. This suppression was associated with potent induction of a type 2 cytokine response characterized by coexpression of interleukin-4 (IL-4) and IL-10 by CD4(+) T cells, downregulation of proinflammatory cytokine expression in the draining lymph nodes and the colon, and recruitment of alternatively activated (M2) macrophages and eosinophils to the site of ES administration. Protease digestion and heat denaturation of AcES resulted in impaired induction of CD4(+) IL-4(+) IL-10(+) cell responses and diminished ability to suppress colitis, indicating that protein component(s) are responsible for some of the immunosuppressive effects of AcES. Identification of the specific parasite-derived molecules responsible for reducing pathology during chemically induced colitis could lead to the development of novel therapeutics for the treatment of human inflammatory bowel disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ancylostoma / immunology
  • Ancylostoma / metabolism*
  • Animals
  • CD4-Positive T-Lymphocytes / classification
  • CD4-Positive T-Lymphocytes / metabolism*
  • Colitis / chemically induced
  • Colitis / drug therapy
  • Colitis / pathology*
  • Colon / immunology
  • Colon / pathology
  • Cytokines / metabolism
  • Dextran Sulfate / toxicity
  • Eosinophils / cytology
  • Female
  • Helminth Proteins / pharmacology*
  • Helminth Proteins / therapeutic use
  • Interleukin-10 / metabolism*
  • Interleukin-4 / metabolism*
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Macrophages / cytology
  • Mice
  • Mice, Inbred C57BL
  • Peritoneal Cavity / cytology


  • Cytokines
  • Helminth Proteins
  • IL10 protein, mouse
  • Interleukin-10
  • Interleukin-4
  • Dextran Sulfate