Eosinophils, basophils and myeloid-derived suppressor cells in chronic Loa loa infection and its treatment in an endemic setting.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101291488 Publication Model: eCollection Cited Medium: Internet ISSN: 1935-2735 (Electronic) Linking ISSN: 19352727 NLM ISO Abbreviation: PLoS Negl Trop Dis Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Loiasis*/drug therapy ; Loiasis*/immunology ; Eosinophils*/immunology ; Basophils*/immunology ; Loa*/physiology ; Loa*/immunology ; Myeloid-Derived Suppressor Cells*/immunology; Humans ; Male ; Female ; Adult ; Gabon/epidemiology ; Animals ; Middle Aged ; Young Adult ; Albendazole/therapeutic use ; Chronic Disease ; Flow Cytometry ; Cytokines ; Endemic Diseases ; Adolescent

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.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AAA is a member of the CANTAM (EDCTP-RegNet2015-1045) network. The authors have declared that no competing interests exist.
(Copyright: © 2024 Burger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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F4216019LN (Albendazole)
0 (Cytokines)

Date Created: 20240521 Date Completed: 20240603 Latest Revision: 20240605

20250114

PMC11147522

10.1371/journal.pntd.0012203

38771861