Expression of interleukin 4, interleukin 4 splice variants and interferon gamma mRNA in calves experimentally infected with Fasciola hepatica

• Published in: Veterinary immunology and immunopathology 2004, Vol.97 (1), p.53-63
• Main Authors: Waldvogel, A.S., Lepage, M.-F., Zakher, A., Reichel, M.P., Eicher, R., Heussler, V.T.
• Format: Article
• Language: English
• Subjects: Alternative Splicing - genetics; Alternative Splicing - immunology; Animals; Antibodies, Helminth - blood; Bovine; Cattle; Cattle Diseases - immunology; Cattle Diseases - metabolism; Cattle Diseases - parasitology; Enzyme-Linked Immunosorbent Assay - veterinary; Fasciola hepatica; Fasciola hepatica - genetics; Fasciola hepatica - immunology; Fascioliasis - immunology; Fascioliasis - metabolism; Fascioliasis - parasitology; Fascioliasis - veterinary; Feces - parasitology; Gene Expression Regulation - immunology; Interferon γ; Interferon-gamma - biosynthesis; Interferon-gamma - genetics; Interferon-gamma - immunology; Interleukin 4; Interleukin-4 - biosynthesis; Interleukin-4 - genetics; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - parasitology; Male; Parasite Egg Count - veterinary; Reverse Transcriptase Polymerase Chain Reaction - veterinary; RNA, Helminth - chemistry; RNA, Helminth - genetics; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Sequence Analysis, DNA; Splice variant interleukin 4
• ISSN: 0165-2427; 1873-2534
• DOI: 10.1016/j.vetimm.2003.08.002

Interleukin 4 (IL-4) is expected to play a dominant role in the development of T helper (Th) 2 cells. Th2 immune responses with expression of relatively large amounts of interleukin 4 (IL-4) but little interferon γ (IFN-γ) are characteristic for chronic helminth infections. But no information is available about IL4 expression during early Fasciola hepatica ( F. hepatica) infections in cattle. Therefore, we investigated F. hepatica specific IL-4 and IFN-γ mRNA expression in peripheral blood mononuclear cells (PBMCs) from calves experimentally infected with F. hepatica. Cells were collected prior to infection and on post-inoculation days (PIDs) 10, 28 and 70. Interestingly, PBMCs responded to stimulation with F. hepatica secretory–excretory products (FhSEP) already on PID 10 and expressed high amounts of IL-4 but not of IFN-γ mRNA suggesting that F. hepatica induced a Th2 biased early immune response which was not restricted to the site of infection. Later in infection IL-4 mRNA expression decreased whereas IFN-γ mRNA expression increased slightly. Isolated lymph node cells (LNCs) stimulated with FhSEP and, even more importantly, non-stimulated LN tissue samples indicated highly polarized Th2 type immune responses in the draining (hepatic) lymph node, but not in the retropharyngeal lymph node. During preliminary experiments, two splice variants of bovine IL-4 mRNA, boIL-4δ2 and boIL-4δ3, were detected. Since a human IL-4δ2 was assumed to act as competitive inhibitor of IL-4, it was important to know whether expression of these splice variants of bovine IL-4 have a regulatory function during an immune response to infection with F. hepatica. Indeed, IL-4 splice variants could be detected in a number of samples, but quantitative analysis did not yield any clue to their function. Therefore, the significance of bovine IL-4 splice variants remains to be determined.