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

Abstract

This study investigated the effect of maternal Onchocerca volvulus infection on humoral and cellular responsiveness in newborn children and their mothers. Onchocerca volvulus-specific IgG isotypes and IgE were significantly elevated in infected mothers and their infants. One year post partum, O. volvulus-specific IgG4 was strongly reduced in children of infected mothers, while IgG1 responses weakened only slightly. Umbilical cord mononuclear blood cells (UCBC) and peripheral blood cells (PBMC) from mothers proliferated in response to phytohaemagglutinin (PHA), concanavalin A (Con A), and the bacterial 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 micrograms/ml), PPD (at 10 and 50 micrograms/ml) and O. volvulus-derived antigens (OvAg) (at 35 micrograms/ml), and in parallel, a diminished cellular reactivity (P < 0.01) by PBMC was observed to OvAg in mothers positive 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 OvAg, bacterial SL-O and PHA. OvAg did not stimulate IL-2 and none of the mitogens or antigens induced production of IL-4 in neonates. In response to OvAg, substantially elevated (P < 0.01) amounts of IFN-gamma were produced by UCBC from newborns of O. volvulus-infected mothers. UCBC secreted low levels 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. volvulus-infection will sensitize in utero parasite-specific cellular immune responsiveness in neonates and activate OvAg-specific production of several Th1- and Th2-type cytokines.

Association of In Utero Sensitization to Schistosoma haematobium with Enhanced Cord Blood IgE and Increased Frequencies of CD5– B Cells in African Newborns

“…3,4,6,7,19 The intravascular location of schistosomes ensures that antigens excreted or secreted by worms and eggs directly enter the maternal vasculature. 14,26,37 These antigens may thus reach the placenta and the fetal vessels.…”

“…It has previously been shown that in disease-endemic countries total 3,7,10,12 and filarial antigen-specific 3,7,10,12 fetal IgE production occurs. Only one investigation 6 demonstrated a direct correlation of enhanced cord blood helminth antigen-specific IgE levels with the corresponding maternal helminth (Onchocerca volvolus) infection, and other studies found no correlation. 7,10 There are few studies regarding the priming of the fetal humoral immune system as a result of maternal schistosome infection.…”

“…However, there is increasing evidence of in utero sensitization as a result of maternal helminth infections. [2][3][4][5][6][7] The question of how infections and/or microbial products in the mother might affect the development of the fetal immune system is of particular interest because it may explain disease patterns later in life.…”

“…Some studies have suggested that prenatal priming might be beneficial and lead to protection against infections or to reduced pathologic changes, [2][3][4][5][6]8 and other studies have suggested that prenatal exposure might be detrimental and lead to development of allergic responses 3,9 or to unresponsiveness 3,8,10,11 and therefore inadequate reactivity of the immune system to infections or immunizations. 8,12,13 It has also been suggested that prenatal sensitization rather than exposure to helminths during childhood is important in determining the initial immune response elicited by natural infection.…”

“…In areas where these parasites are endemic, pregnant women often harbor these infections. 6,10,14,15 Because IgE and IgM isotypes normally do not cross the placental barrier, 3,6,16 the presence of these antibodies in umbilical cord blood is evidence of prenatal priming. It has previously been shown that in disease-endemic countries total 3,7,10,12 and filarial antigen-specific 3,7,10,12 fetal IgE production occurs.…”