Intestinal Polyparasitism Is Associated with PPD-Stimulated Regulatory Cytokine Responses in Bolivian Highland Schoolchildren

Micronutrient deficiencies and parasitic infections are prevalent in low-resource settings, but their relative impact on functional cellular immunity in high-altitude environments remains poorly understood. We evaluated the ex vivo cytokine responses of whole blood to mitogenic phytohemagglutinin (PHA) and antigenic purified protein derivative (PPD) stimulation in 187 Bolivian children aged 5–13 years from the highlands. We assessed the relationship between these responses and parasitic burden and composite micronutrient status (vitamin A, vitamin D and zinc). The cohort exhibited a high prevalence of protozoa (Entamoeba coli 51.3%, Blastocystis hominis 45.5%, Giardia lamblia 31.0%) alongside the helminth Hymenolepis nana (25.7%). Substantial micronutrient deficiency was also evident (vitamin D 53.3%, vitamin A 43.8%, zinc 17.4%). Surprisingly, composite micronutrient deficiency had no significant effect on cytokine production. Instead, vigorous cellular activation was observed across all groups relative to unstimulated controls (p < 0.001). Parasitic infection was associated with higher IL-10 production, which was borderline significant under PHA stimulation (p = 0.050) and more evident under PPD stimulation (p < 0.001). The IL-10/IFN-γ regulatory index (RI) was significantly elevated by parasitic richness specifically under PPD stimulation (p = 0.002), while no parasite-driven changes were observed for IFN-γ under either PHA or PPD stimulation. Under PPD stimulation, children with a protozoan infection only had higher IL-10 levels than uninfected children (median 408.0 vs. 284.0; p = 0.001). These findings suggest that protozoan infection is associated with enhanced regulatory cytokine responses during PPD stimulation in schoolchildren from the Bolivian Highlands. In this setting, protozoan species richness, rather than nutritional status, conditions the regulatory tone of the antigen-specific immune response.