title: Down-regulated lymphoproliferation coincides with parasite maturation and with the collapse of both gamma interferon and interleukin-4 responses in a bovine model of onchocerciasis.
abstract: Onchocerciasis is a debilitating parasitic infection caused by the filarial nematode Onchocerca volvulus. Infections are chronic, and persistence of the parasites for several years argues for highly adapted mechanisms of immune evasion. Due to the restricted host repertoire of O. volvulus, we have used the cattle parasite Onchocerca ochengi to investigate the nature of immunomodulation underpinning these long-term infections. Cattle were infected with a single inoculation of 350 infective-stage larvae under laboratory conditions (n = 6). Intradermal nodules containing immature adult worms were detected from 110 days postinfection, and microfilariae in skin were detected from day 280 postinfection. Parasite-specific responses during early infection were nonpolarized with respect to the major Th cytokines (interleukin-4 [IL-4], IL-2, and gamma interferon [IFN-gamma]) produced by antigen-stimulated peripheral blood mononuclear cells (PBMC) or serum antibody isotypes. Antigen-induced proliferation of PBMC peaked shortly after exposure and remained high during the prepatent infection. As the parasites matured and animals developed patent infections, there was a profound down-regulation of lymphoproliferation, accompanied by sharp falls in the expression of both IL-4 and IFN-gamma and a gradual decline in IL-2. Levels of immunoglobulin G2 (IgG2) fell, while those of IgG1 remained high. We conclude that neither a classical Th2 response nor a simple Th1-to-Th2 switch is sufficient to explain the immunomodulation associated with patent Onchocerca infections. Instead, there is an initial Th0 response, which matures into a response with some, but not all of the features of a Th2 response. The natural host-parasite relationship of O. ochengi in cattle may be useful as both a descriptive and predictive tool to test more refined models of immunomodulation in onchocerciasis.
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom. sgraham@cgiar.org
authors.forename: S P
authors.initials: SP
authors.lastname: Graham
authors.forename: A J
authors.initials: AJ
authors.lastname: Trees
authors.forename: R A
authors.initials: RA
authors.lastname: Collins
authors.forename: D M
authors.initials: DM
authors.lastname: Moore
authors.forename: F M
authors.initials: FM
authors.lastname: Guy
authors.forename: M J
authors.initials: MJ
authors.lastname: Taylor
authors.forename: A E
authors.initials: AE
authors.lastname: Bianco
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D009854:Onchocerca / Q000254:growth & development / Q000276:immunology; D009855:Onchocerciasis / Q000276:immunology*
chemical_list: D000909:Antibodies, Helminth; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma