Down-regulated lymphoproliferation coincides with parasite maturation and with the collapse of both gamma interferon and interleukin-4 responses in abovine model of onchocerciasis

Onchocerciasis is a debilitating parasitic infection caused by the filarial nematode Onchocerca volvulus, Infections are chronic, and persistence of t he parasites for several years argues for highly adapted mechanisms of immu ne evasion. Due to the restricted host repertoire of O. volvulus, we have u sed the cattle parasite Onchocerca ochengi to investigate the nature of imm unomodulation underpinning these Long-term infections. Cattle were infected with a single inoculation of 350 infective-stage larvae under laboratory c onditions (n = 6), Intradermal nodules containing immature adult worms were detected from 110 days postinfection, and microfilariae in skin were detec ted from day 280 postinfection, Parasite-specific responses during early in fection were nonpolarized with respect to the major Th cytokines (interleuk in-4 [IL-4], IL-2, and gamma interferon [IFN-gamma]) produced by antigen-st imulated peripheral blood mononuclear cells (PBMC) or serum antibody isotyp es, 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 bot h IL-4 and IFN-gamma and a gradual decline in IL-2, Levels of immunoglobuli n G2 (IgG2) fell, while those of IgG1 remained high. We conclude that neith er 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 w ith some, but not all of the features of a Th2 response. The natural host-p arasite relationship of O. ochengi in cattle may be useful as both a descri ptive and predictive tool to test more refined models of immunomodulation i n onchocerciasis.