Prenatal immune priming with helminth infections: parasite-specific cellular reactivity and Th1 and Th2 cytokine responses in neonates

The present investigation aimed to determine to what extent maternal helmin th infection primes parasite-specific cellular responsiveness in neonates. Umbilical cord mononuclear blood cells (UCBC) and peripheral blood mononucl ear cells (PBMC) from mothers proliferated in response to mitogenic stimula tion with concanavalin A, as well as to bacterial Streptococcus pyogenes-de rived (streptolysin O) and helminth-specific antigens of Necator americanus and Onchocerca volvulus. Cellular responses to Echinococcus multilocularis (Em) and Oesophagostonmum bifurcum (Oes), helminth parasites not endemic i n the study area, were absent (for Em) or very low (for Oes due to antigeni c cross-reactivity). Cellular responsiveness to mitogen and antigens was hi gher in mothers than in their neonates. Several Th1-type (IL-2, IL-12, and IFN-gamma) and Th2-type (IL-5 and IL-IO) cytokines were produced by UCBC fr om neonates and PBMC from mothers. Low levels of IFN-gamma were elicited by UCBC in response to helminth and bacterial antigens, while secretion of IL -2 was pronounced and similarly high in neonates and their mothers. Amounts of IL-5 produced by UCBC in response to bacterial SL-O and mitogenic stimu lation (PHA) were low, but equivalent levels of IL-5 were induced by intest inal helminth and filaria-derived antigens in neonates and mothers. A prono unced production of IL-10 and IL-12 by UCBC was observed - spontaneous IL-1 0 and IL-12 secretion by UCBC was higher in neonates than by PBMC from moth ers. Net amounts of IL-10 elicited by helminth antigens were similar, while net IL-12 in response to mitogen, and bacterial and helminth antigens was significantly higher in mothers than their offspring. Our results indicate that human maternal helminth infection does sensitize in utero for parasite -specific cellular responsiveness in offspring, and also activates specific production of several cytokines, and such children do not present a domina nt expression of immunity of either Th1 or Th2.