TY - BOOK

T1 - Expulsion of the swine whipworm, Trichuris suis 

T2 - a study of the immune mechanisms involved

AU - Kringel, Helene

PY - 2007

Y1 - 2007

N2 - The whipworm of swine, Trichuris suis, is a gastrointestinal nematode that lives attached to the large intestinal mucosa of its host. Except for when infection levels are high, this parasite rarely causes disease in pigs. Nevertheless, increased interest in T. suis has arisen from studies demonstrating the potential use of its eggs as immunomodulators, treating patients suffering from inflammatory bowel disease and possibly other autoimmune diseases. The immune response induced by T. suis in its host and particularly, the resulting expulsion of worms is the focus of this thesis. Whipworms in mice, Trichuris muris, have been extensively studied and in this model it is well established that Trichuris induces a protective T helper cell type (Th) 2-associated immune response that in resistant strains results in expulsion of worms. A similar immune response was believed to be induced in T. suis infected pigs, but it has yet to be verified.The expulsion of T. suis was confirmed to take place around 9 weeks post infection (p.i.) by quantifying worm burdens in serially necropsied T. suis infected pigs. In order to identify changes in the pigs of possible importance for expulsion, several different parasitological, immunological and pathological parameters were evaluated in the T. suis infected pigs during the course of infection. T. suis infections were found to be associated with increases in specific serum antibodies, blood eosinophilia and basophilia, eosinophil and mast cell infiltrations of the colon mucosa, colon crypt hyperplasia and colon mucosa hypertrophy. Gene expression analysis of genes related to immune function revealed a local Th2-like gene-expression pattern with up-regulated levels of the key cytokines IL-4, -5 and -13 that peaked 5-7 weeks p.i.. Several of the parameters seemed to be closely associated with the presence of worms. The results from an extended gene expression analysis of different tissues from T. suis infected pigs have been included as well. These demonstrate expression of novel Th2 associated genes, of which some are closely associated with the level of worm burden.Overall, it was confirmed that T. suis induces a Th2-skewed immune response that fits well into the current hypothesis of Trichuris expulsion obtained from mouse models. Complementary to the highly inbred mouse models, pigs can arguably be considered a good large animal model for T. suis egg treated humans, as pigs closely resemble humans in intestinal anatomy and physiology and in immune functions.

AB - The whipworm of swine, Trichuris suis, is a gastrointestinal nematode that lives attached to the large intestinal mucosa of its host. Except for when infection levels are high, this parasite rarely causes disease in pigs. Nevertheless, increased interest in T. suis has arisen from studies demonstrating the potential use of its eggs as immunomodulators, treating patients suffering from inflammatory bowel disease and possibly other autoimmune diseases. The immune response induced by T. suis in its host and particularly, the resulting expulsion of worms is the focus of this thesis. Whipworms in mice, Trichuris muris, have been extensively studied and in this model it is well established that Trichuris induces a protective T helper cell type (Th) 2-associated immune response that in resistant strains results in expulsion of worms. A similar immune response was believed to be induced in T. suis infected pigs, but it has yet to be verified.The expulsion of T. suis was confirmed to take place around 9 weeks post infection (p.i.) by quantifying worm burdens in serially necropsied T. suis infected pigs. In order to identify changes in the pigs of possible importance for expulsion, several different parasitological, immunological and pathological parameters were evaluated in the T. suis infected pigs during the course of infection. T. suis infections were found to be associated with increases in specific serum antibodies, blood eosinophilia and basophilia, eosinophil and mast cell infiltrations of the colon mucosa, colon crypt hyperplasia and colon mucosa hypertrophy. Gene expression analysis of genes related to immune function revealed a local Th2-like gene-expression pattern with up-regulated levels of the key cytokines IL-4, -5 and -13 that peaked 5-7 weeks p.i.. Several of the parameters seemed to be closely associated with the presence of worms. The results from an extended gene expression analysis of different tissues from T. suis infected pigs have been included as well. These demonstrate expression of novel Th2 associated genes, of which some are closely associated with the level of worm burden.Overall, it was confirmed that T. suis induces a Th2-skewed immune response that fits well into the current hypothesis of Trichuris expulsion obtained from mouse models. Complementary to the highly inbred mouse models, pigs can arguably be considered a good large animal model for T. suis egg treated humans, as pigs closely resemble humans in intestinal anatomy and physiology and in immune functions.

KW - Former LIFE faculty

KW - Trichuris suis

KW - piskeorm

KW - udstødelse

KW - Immun respons

KW - gris

KW - tarm

KW - Trichuris suis

KW - whipworm

KW - expulsion

KW - Immune response

KW - pig

KW - intestine

M3 - Ph.D. thesis

SN - 978-87-7611-199-1

BT - Expulsion of the swine whipworm, Trichuris suis 

PB - Center for Skov, Landskab og Planlægning/Københavns Universitet

CY - Frederiksberg, Danmark

ER -