The gastrointestinal nematode Trichostrongylus colubriformis down-regulates immune gene expression in migratory cells in afferent lymph

BMC Immunol. 2010 Oct 17:11:51. doi: 10.1186/1471-2172-11-51.

Abstract

Background: Gastrointestinal nematode (GIN) infections are the predominant cause of economic losses in sheep. Infections are controlled almost exclusively by the use of anthelmintics which has lead to the selection of drug resistant nematode strains. An alternative control approach would be the induction of protective immunity to these parasites. This study exploits an ovine microarray biased towards immune genes, an artificially induced immunity model and the use of pseudo-afferent lymphatic cannulation to sample immune cells draining from the intestine, to investigate possible mechanisms involved in the development of immunity.

Results: During the development of immunity to, and a subsequent challenge infection with Trichostrongylus colubriformis, the transcript levels of 2603 genes of cells trafficking in afferent intestinal lymph were significantly modulated (P < 0.05). Of these, 188 genes were modulated more than 1.3-fold and involved in immune function. Overall, there was a clear trend for down-regulation of many genes involved in immune functions including antigen presentation, caveolar-mediated endocytosis and protein ubiquitination. The transcript levels of TNF receptor associated factor 5 (TRAF5), hemopexin (HPX), cysteine dioxygenase (CDO1), the major histocompatability complex Class II protein (HLA-DMA), interleukin-18 binding protein (IL-18BP), ephrin A1 (EFNA1) and selenoprotein S (SELS) were modulated to the greatest degree.

Conclusions: This report describes gene expression profiles of afferent lymph cells in sheep developing immunity to nematode infection. Results presented show a global down-regulation of the expression of immune genes which may be reflective of the natural temporal response to nematode infections in livestock.

MeSH terms

  • Animals
  • Catheterization
  • Cysteine Dioxygenase / genetics
  • Cysteine Dioxygenase / immunology
  • Cysteine Dioxygenase / metabolism
  • Down-Regulation / immunology*
  • Gastrointestinal Diseases / genetics
  • Gastrointestinal Diseases / immunology*
  • Gastrointestinal Diseases / parasitology
  • Gene Expression Profiling
  • Hemopexin / genetics
  • Hemopexin / immunology
  • Hemopexin / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines / immunology
  • Intestines / parasitology
  • Intestines / pathology
  • Lymph / cytology
  • Lymph / immunology
  • Lymph / metabolism*
  • Lymph / parasitology
  • Protein Array Analysis
  • Sheep
  • TNF Receptor-Associated Factor 5 / genetics
  • TNF Receptor-Associated Factor 5 / immunology
  • TNF Receptor-Associated Factor 5 / metabolism
  • Trichostrongylosis / genetics
  • Trichostrongylosis / immunology*
  • Trichostrongylosis / parasitology
  • Trichostrongylus / immunology*

Substances

  • TNF Receptor-Associated Factor 5
  • Hemopexin
  • Cysteine Dioxygenase