T Cell Activation in South African HIV-Exposed Infants Correlates with Ochratoxin A Exposure

Abstract

The introduction of non-breastmilk foods to HIV-infected infants is associated with increased levels of immune activation, which can impact the rate of HIV disease progression. This is particularly relevant in countries where mother-to-child transmission of HIV still occurs at unacceptable levels. The goal of this study was to evaluate the levels of the toxic food contaminant ochratoxin A (OTA) in HIV-exposed South African infants that are either breastfed or consuming non-breast milk foods. OTA is a common mycotoxin, found in grains and soil, which is toxic at high doses but has immunomodulatory properties at lower doses. Samples from HIV-exposed and HIV-unexposed infants enrolled in prospective observational cohort studies were collected and analyzed at birth through 14 weeks of age. We observed that infants consuming non-breast milk foods had significantly higher plasma levels of OTA at 6 weeks of age compared to breastfed infants, increasing until 8 weeks of age. The blood levels of OTA detected were comparable to levels observed in OTA-endemic communities. OTA plasma levels correlated with HIV target cell activation (CCR5 and HLADR expression on CD4+ T cells) and plasma levels of the inflammatory cytokine CXCL10. These findings provide evidence that elevated OTA levels in South African infants are associated with the consumption of non-breastmilk foods and activation of the immune system. Reducing infant OTA exposure has the potential to reduce immune activation and provide health benefits, particularly in those infants who are HIV-exposed or HIV-infected.

Mycotoxin Occurrence, Exposure and Health Implications in Infants and Young Children in Sub-Saharan Africa: A Review

“…Earlier studies by this group of authors observed a remarkable increase in IYC exposure to AFs following the introduction of and increase in the consumption of weaning foods [34,126]. Similar results were reported in a South African study on non-breastfed infants [136]. Significant levels of OTA were detected in the plasma of non-breastfed infants at 6 weeks old as compared to breastfed infants.…”

“…While cancer is rare in children, studies have linked exposures to environmental toxins in the perinatal period as a major causative agent of genetic diseases, such as cancer, in adulthood [210]. Thus, the frequency of mycotoxin occurrence in foods for infants and young children and mycotoxin exposure of this group, as highlighted in this review, should not be ignored [74,98,120,130,133,136].…”

“…Other West African studies, specifically in Ghana, showed the potential effects of AF exposure on immune responses of HIV-positive participants [167][168][169][170], and tuberculosis patients [171], however, no such study on the infant population in these regions has been reported. Another study investigated the effect of OTA on T cell activation using a cohort of South African HIV-exposed infants and HIV-unexposed infants as controls [136]. The authors observed a correlation of OTA plasma levels with the activation of CD4 T cells (HLADR and CCR5) and a chemokine, CXCL10.…”

“…The authors observed a correlation of OTA plasma levels with the activation of CD4 T cells (HLADR and CCR5) and a chemokine, CXCL10. Increased expression of CXCL10, HLA-DR, and CCR5 has been associated with a variety of human diseases, including HIV, immune dysfunction, chronic inflammation, infectious diseases, tumour development, and encephalopathy, known as a major cause of infant mortality in Africa [136,[172][173][174], thus suggesting an increased risk of morbidity and mortality due to OTA exposure.…”

Mold, Mycotoxins and a Dysregulated Immune System: A Combination of Concern?

“…Furthermore, the mycotoxin ochratoxin A (OTA) mainly occurring in cereals, coffee, and red wine, has been reported to affect immunological response in piglets [43]. In humans, it is predominantly known for its acute nephrotoxic effect and a range of chronic disorders like upper urothelial carcinoma [44], but also immunomodulatory effects are under discussion [45].…”