Prenatal immune priming in onchocerciasis - Onchocerca volvulus-specific cellular responsiveness and cytokine production in newborns from infected mothers

This study investigated the effect of maternal Onchocerca volvulus infectio n on humoral and cellular responsiveness in newborn children and their moth ers. Onchocerca volvulus-specific IgG isotypes and IgE were significantly e levated in infected mothers and their infants. One year post partum, O. vol vulus-specific IgG4 was strongly reduced in children of infected mothers, w hile IgG1 responses weakened only slightly. Umbilical cord mononuclear bloo d cells (UCBC) and peripheral blood cells (PBMC) from mothers proliferated in response to phytohaemagglutinin (PHA), concanavalin A (Con A), and the b acterial antigens streptolysin-O (SL-O) or purified protein derivative (PPD ). UCBC from neonates born to O. volvulus-infected mothers responded lower (P < 0.01) to Con A (at 5 mu g/ml), PPD (at 10 and 50 mu g/ml) and O. volvu lus-derived antigens (OvAg) (at 35 mu g/ml), and in parallel, a diminished cellular reactivity (P < 0.01) by PBMC was observed to OvAg in mothers posi tive for O. volvulus. Several Th1-type (IL-2, IL-12, interferon-gamma (IFN- gamma) and tumour necrosis factor-alpha (TNF-alpha)) and Th2-type (IL-4, IL -5, IL-10, IL-13) cytokines were secreted by UCBC and PBMC in response to O vAg, bacterial SL-O and PHA. OvAg did not stimulate IL-2 and none of the mi togens or antigens induced production of IL-4 in neonates. In response to O vAg, substantially elevated (P < 0.01) amounts of IFN-gamma were produced b y UCBC from newborns of O. volvulus-infected mothers. UCBC secreted low lev els of IL-5 and IL-13, while higher amounts of IL-10 were found (P < 0.01) in newborns from onchocerciasis-free mothers. In conclusion, maternal O. vo lvulus-infection will sensitize in utero parasite-specific cellular immune responsiveness in neonates and activate OvAg-specific production of several Th1- and Th2-type cytokines.