Reductions in microfilaridermia by repeated ivermectin treatment are associated with lower Plasmodium-specific Th17 immune responses in Onchocerca volvulus-infected individuals

Kathrin Arndts, Ute Klarmann-Schulz, Linda Batsa, Alexander Y Debrah, Christian Epp, Rolf Fimmers, Sabine Specht, Laura E Layland, Achim Hoerauf

37 million individuals are currently infected with Onchocerca volvulus (O. volvulus), a parasitic nematode that elicits various dermal manifestations and eye damage in man. Disease control is primarily based on distributing ivermectin in mass drug administration (MDA) programmes which aim at breaking transmission by eliminating microfilariae (MF), the worm's offspring. The majority of infected individuals present generalized onchocerciasis, which is characterized by hyporesponsive immune responses and high parasite burden including MF. Recently, in areas that have been part of MDA programmes, individuals have been identified that present nodules but are amicrofilaridermic (a-MF) and our previous study showed that this group has a distinct immune profile. Expanding on those findings we determined the immune responses of O. volvulus-infected individuals to a Plasmodium-derived antigen MSP-1 (merozoite surface protein-1), which is required by the parasite to enter erythrocytes. Isolated PBMCs from O. volvulus-infected individuals (164 MF(+) and 46 a-MF) and non-infected volunteers from the same region (NEN), were stimulated with MSP-1 and the resulting supernatant screened for the presence of IL-5, IL-13, IFN-γ, TNF-α, IL-6, IL-17A and IL-10. These findings were then further analyzed following regression analysis using the covariates MF, ivermectin (IVM) and region. The latter referred to the Central or Ashanti regions of Ghana, which, at the time sampling, had received 8 or 1 round of MDA respectively. IL-5, IL-13 and IFN-γ responses to MSP-1 were not altered between NEN and O. volvulus-infected individuals nor were any associations revealed in the regression analysis. IL-10, IL-6 and TNF-α MSP-1 responses were, however, significantly elevated in cultures from infected individuals. Interestingly, when compared to a-MF individuals, MSP-induced IL-17A responses were significantly higher in MF(+) patients. Following multivariable regression analysis these IL-10, IL-6, TNF-α and IL-17A responses were all dominantly associated with the regional covariate. Consequently, areas with a lowered infection pressure due to IVM MDA appear to influence bystander responses to Plasmodium-derived antigens in community members even if they have not regularly participated in the therapy.