부산대학교 도서관

Background: Chronic infection by Loa loa remains an unsolved immunological paradox. Despite harboring subcutaneously migrating adult worms and often high densities of microfilariae, most patients experience only relatively mild symptoms, yet microfilaricidal treatment can trigger life-threatening inflammation. Here, we investigated innate cell populations hypothesized to play a role in these two faces of the disease, in an endemic population in Gabon. Methodology/Principal findings: We analyzed numbers and activation of eosinophils and basophils, as well as myeloid-derived suppressor cell (MDSC) subsets and associated circulating cytokine levels by flow cytometry in sex- and age-matched L. loa-uninfected (LL-), -amicrofilaraemic (MF-) and -microfilaraemic (MF+) individuals (n = 42), as well as microfilaraemic individuals treated with albendazole (n = 26). The percentage of eosinophils was lower in LL- (3.0%) than in the combined L. loa-infected population, but was similar in MF+ (13.1%) and MF- (12.3%). Upon treatment of MF+, eosinophilia increased from day 0 (17.2%) to day 14 (24.8%) and had decreased below baseline at day 168 (6.3%). Expression of the eosinophil activation marker CD123 followed the same pattern as the percentage of eosinophils, while the inverse was observed for CD193 and to some extent CD125. Circulating IL-5 levels after treatment followed the same pattern as eosinophil dynamics. Basophil numbers did not differ between infection states but increased after treatment of MF+. We did not observe differences in MDSC numbers between infection states or upon treatment. Conclusions/Significance: We demonstrate that both chronic infection and treatment of L. loa microfilaraemia are associated with eosinophil circulation and distinct phenotypical activation markers that might contribute to inflammatory pathways in this setting. In this first ever investigation into MDSC in L. loa infection, we found no evidence for their increased presence in chronic loiasis, suggesting that immunomodulation by L. loa is induced through other pathways. Author summary: Loiasis–also called African eye worm for its most pathognomonic feature–is a disease caused by the helminth Loa loa, affecting over ten million people in Central and West Africa. While L. loa seems to successfully evade an effective immune response in chronic infection, treatment can lead to severe inflammation upon rapid death of L. loa larvae in the blood. Here, we investigated different subsets of immune cells hypothesized to play a role in L. loa-mediated immune modulation in chronically infected individuals and upon treatment of individuals with circulating larvae. We found that eosinophils–an important cell population in the immune response to helminths–increase in numbers and are activated in both L. loa-infection and its treatment. Myeloid-derived suppressor cells can suppress immune responses in cancer and some other infectious diseases but have never been investigated in loiasis. We hypothesized that they are involved in immunosuppression by L. loa but found no evidence thereof. Better understanding of immunomodulation in chronic loiasis may ultimately improve the management of this neglected disease. [ABSTRACT FROM AUTHOR]