Circulating IL-6, IL-10, and TNF-alpha and IL-10/IL-6 and IL-10/TNF-alpha ratio profiles of polyparasitized individuals in rural and urban areas of gabon

PLoS Negl Trop Dis. 2022 Apr 14;16(4):e0010308. doi: 10.1371/journal.pntd.0010308. eCollection 2022 Apr.

Abstract

Malaria, blood-borne filarial worms and intestinal parasites are all endemic in Gabon. This geographical co-distribution leads to polyparasitism and, consequently, the possibility of immune-mediated interactions among different parasite species. Intestinal protozoa and helminths could modulate antimalarial immunity, for example, thereby potentially increasing or reducing susceptibility to malaria. The aim of the study was to compare the cytokine levels and cytokine ratios according to parasitic profiles of the population to determine the potential role of co-endemic parasites in the malaria susceptibility of populations. Blood and stool samples were collected during cross-sectional surveys in five provinces of Gabon. Parasitological diagnosis was performed to detect plasmodial parasites, Loa loa, Mansonella perstans, intestinal helminths (STHs) and protozoan parasites. Nested PCR was used to detect submicroscopic plasmodial infection in individuals with negative blood smears. A cytometric bead array was used to quantify interleukin (IL)-6, IL-10 and tumour necrosis factor (TNF)-α in the plasma of subjects with different parasitological profiles. Median IL-6 and IL-10 levels and the median IL-10/TNF-α ratio were all significantly higher among individuals with Plasmodium (P.) falciparum infection than among other participants (p<0.0001). The median TNF-α level and IL-10/IL-6 ratio were higher in subjects with STHs (p = 0.09) and P. falciparum-intestinal protozoa co-infection (p = 0.04), respectively. IL-6 (r = -0.37; P<0.01) and IL-10 (r = -0.37; P<0.01) levels and the IL-10/TNF-α ratio (r = -0.36; P<0.01) correlated negatively with age. Among children under five years old, the IL-10/TNF-α and IL-10/IL-6 ratios were higher in those with intestinal protozoan infections than in uninfected children. The IL-10/TNF-α ratio was also higher in children aged 5-15 years and in adults harbouring blood-borne filariae than in their control counterparts, whereas the IL-10/IL-6 ratio was lower in those aged 5-15 years with filariae and intestinal parasites but higher in adults with intestinal parasitic infections. Asymptomatic malaria is associated with a strong polarization towards a regulatory immune response, presenting high circulating levels of IL-10. P. falciparum/intestinal protozoa co-infections were associated with an enhanced IL-10 response. Immunity against malaria could differ according to age and carriage of other parasites. Helminths and intestinal protozoa can play a role in the high susceptibility to malaria currently observed in some areas of Gabon, but further investigations are necessary.

MeSH terms

  • Animals
  • Child, Preschool
  • Cities / epidemiology
  • Coinfection* / epidemiology
  • Coinfection* / parasitology
  • Cross-Sectional Studies
  • Cytokines / blood
  • Gabon / epidemiology
  • Humans
  • Interleukins* / blood
  • Malaria* / blood
  • Malaria* / epidemiology
  • Malaria, Falciparum* / blood
  • Malaria, Falciparum* / epidemiology
  • Plasmodium falciparum / isolation & purification
  • Rural Population / statistics & numerical data
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Cytokines
  • Interleukins
  • Tumor Necrosis Factor-alpha

Grant support

The Department of Parasitology-Mycology of Tropical Medicine, the Gabonese Red Cross, the CEGADIS group and the RELACS network are the organizations that funded the project. All funds have been invested in the Ph.D. thesis of NPM. The Department of Parasitology-Mycology of Tropical Medicine allowed to NPM to have salary and to research other source of funding. The Gabonese Red Cross worked with the Department of Parasitology-Mycology of Tropical Medicine to collect data and samples in rural areas of Gabon. The Gabonese Red Cross supported this project providing transport in the field and material for parasitosis diagnosis. The CEGADIS group has been solicited for travel-related expenses in Benin where has been carried out immunological analysis. To finish the RELACS network allowed attending to training workshops. These funders, except The Department of Parasitology-Mycology of Tropical Medicine which is my institution, had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.