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Abstract Background The selection pressure imposed by the parasite has a functional consequence on the immune genes, leading to altered immune function in which regulatory T cells (Tregs) induced by parasites during infectious challenges modulate or thwart T effector cell mechanism. Methods We identified and investigated regulatory polymorphisms in the immune gene IL2 and its receptor IL2R alpha (also known as CD25) in Gabonese individuals exposed to plentiful parasitic infections. Results We identified two reported variants each for IL2 and its receptor IL2R alpha gene loci. Also identified were two novel variants, -83 /-84 CT deletions (ss410961576) for IL2 and -409C/T (ss410961577) for IL2R alpha. We further validated all identified promoter variants for their allelic gene expression using transient transfection assays. Three promoter variants of the IL2 locus revealed no significant expression of the reporter gene. The identified novel variant (ss410961577C/T) of the IL2R alpha revealed a significant higher expression of the reporter gene in comparison to the major allele (Prs12722616C/T variant of the IL2R alpha locus altered the transcription factor binding site TBP (TATA box binding protein) and C/EBP beta (CCAAT/enhancer binding protein beta) that are believed to regulate the Treg function. Conclusions The identification and validation of such regulatory polymorphisms in the immune genes may provide a basis for future studies on parasite susceptibility in a population where T cell functions are compromised.

SUMMARY The impact of intestinal helminth infection, i.e. Ascaris lumbricoides and Trichuris trichiura, on cellular responsiveness and cytokine production was investigated in young adults. Ascaris-specific cellular responsiveness was higher in parasite-free endemic controls than in patients infected with T. trichiura, or A. lumbricoides, or patients co-infected with both parasites. Also, mitogen-induced tumour necrosis factor (TNF)-α, interleukin (IL)-12 and interferon (IFN)-γ secretion by peripheral blood mononuclear cells (PBMC) was higher in negative endemic controls than in infected individuals. Ascaris antigen-specific production of TNF-α, IL-12 and IFN-γ was low in singly Ascaris as well as in co-infected patients, whereas secretion of IL-10 and IL-13 was elevated and similarly high in all patient groups. The detection of Trichuris-specific and Ascaris-specific IgG4 revealed significantly higher serum antibody levels in Trichuris or Ascaris patients when compared to endemic controls ( P < 0·05), whereas parasite-specific IgE antibody levels were similarly high in infected individuals and in endemic controls. In summary, chronically infected Ascaris and Trichuris patients with a high parasite load presented reduced cellular reactivity and lower type 1 TNF-α, IFN-γ and IL-12 responses when compared with endemic controls, whereas type 2 IL-10 and IL-13 productions were similar in all groups from the endemic area. The former may support parasite persistence, whereas substantial type 2 cytokine release may promote protective immunity, suggesting an adaptation of the host to control the parasite burden while minimizing immune-mediated host self-damage. [ABSTRACT FROM AUTHOR]

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 μg/ml), PPD (at 10 and 50 μg/ml) and O. volvulus-derived antigens (OvAg) (at 35 μg/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-γ) and tumour necrosis factor-alpha (TNF-α)) 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-γ 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. [ABSTRACT FROM AUTHOR]

Peripheral blood mononuclear cells (PBMC) from 8 onchocerciasis patients, treated or not with ivermectin, were analyzed for phenotypic cell surface markers. A significant increase (P < .05) in γ/δ T cells expressing the Vδ1 chain compared with normal and endemic controls was detected in all patients. PBMC populations from onchocerciasis patients were not expanded after restimulation with Onchocerca volvulus antigens in vitro, but both Vδ1 and Vδ2T cells from normal donors were increased significantly in response to O. volvulus and Mycobacterium tuberculosis (P < .05), respectively. Frozen sections of all 5 onchocerca nodules tested demonstrated an increased number of CD3+ cells in the vicinity of the adult worm, in all cases expressing the α/β T cell receptor and in 2 patients also expressing the γ/δ T cell receptor; 60% of T cells expressed the activation marker Ki67. These data suggest that O. volvulus provides ligands to Vδ1 T cells. [ABSTRACT FROM PUBLISHER]