title: Immunomodulation in chronic Loiasis–Eosinophils, Basophils and Myeloid-Derived Suppressor Cells in Loa loa Infection and its Treatment in an Endemic Setting
Creators: name: Burger, Gerrit Marwin
Publisher: name: Universität Tübingen
Year: 2025
Subjects: subject: 610
subject: Loa loa
subject: Loiasis
subject: Immunology
subject: FOS: Clinical medicine
subject: Filariasis
subject: Helminth
subject: Gabon
subject: Neglected Tropical Diseases
subject: Eosinophils
subject: Basophils
subject: Myeloid-Derived Suppressor Cells

description: Loiasis is a neglected tropical disease caused by the filarial nematode Loa loa. It affects over 10 million people in Central and West Africa, where it causes significant morbidity and mortality. In chronic infection, microfilariae can circulate the blood stream in densities up to over 100,000 mf/ml without causing overt systemic inflammation, suggesting exemplary immunotolerance. However, once highly microfilaraemic individuals are treated, they risk life-threatening hyperinflammatory responses. Here, we hypothesized that chronic Loa loa infection—and microfilaraemic compared to amicrofilaraemic infection—would be associated with immunoregulation mediated by myeloid-derived suppressor cells, while treatment of microfilaraemic individuals would lead to an inflammatory response led by eosinophil and basophil activation. Thus, we investigated these innate immune cell subsets in two human studies in an endemic area in Gabon. We included 42 sex- and age-matched Loa loa-microfilaraemic (MF+), -amicrofilaraemic (MF-) and uninfected (LL-) subjects in a cross-sectional case control study; as well as 26 MF+ individuals receiving different albendazole-based treatment regimens within a randomized controlled trial. Numbers and surface activation markers of eosinophils, basophils and MDSC subsets, as well as associated circulating cytokine levels were assessed by flow cytometry. A T cell proliferation-suppression assay was performed to confirm immunosuppressive capacity of isolated PMN-MDSC from Loa loa-infected participants. Percentage of eosinophils was higher in Loa loa-infected than LL- participants (3.0%) but did not differ significantly between MF+ (13.1%) and MF- (12.3%) individuals. Upon treatment of MF+ subjects, we observed a marked increase in eosinophils between baseline (17.2%) and day 14 (24.8%) of treatment with albendazole, followed by a significant decrease to below baseline until day 168 (6.3%). Similar trends were observed for CD123 expression and circulating IL-5 levels, while opposite patterns evolved for the inverse activation markers CD193 and to some extent CD125. Basophil numbers did not differ between infection states in the cross-sectional study, but increased after treatment, just as basophil CD193 expression. While PMN-MDSC from Loa loa-infected participants were functionally suppressive, we found no difference in neither PMN-MDSC nor M-MDSC numbers between infection states or upon treatment. In contrast to our hypothesis, we did not find evidence for involvement of PMN-MDSC or M-MDSC in immunomodulation by Loa loa, suggesting immune regulation through other pathways. We demonstrate that both chronic Loa loa infection as well as treatment of microfilaraemic loiasis are associated with marked eosinophilia and distinct patterns of phenotypical activation markers that may contribute to inflammatory pathways in these settings. Further unraveling the immunological paradox of Loa loa infection will lead to improved management of this truly neglected disease.