Eosinophils contribute to killing of adult Onchocerca ochengi within onchocercomata following elimination of Wolbachia.
Many filarial nematodes, including Onchocerca volvulus (the cause of human 'River Blindness'), have a mutually dependent relationship with Wolbachia bacteria. There has been much interest in Wolbachia as a chemotherapeutic target, since there are no macrofilaricidal drugs (i.e., lethal to adult worms) of low toxicity. Using the bovine parasite O. ochengi, we previously demonstrated that combined intensive and intermittent (COM) oxytetracycline treatment induces a sustained depletion of Wolbachia and is macrofilaricidal, whereas a short intensive regimen (SIR) is non-macrofilaricidal. To understand how targeting Wolbachia with oxytetracycline can lead to worm death, O. ochengi nodules (onchocercomata) were sequentially excised from cattle administered COM or SIR therapy, and cell infiltrates were microscopically quantified. Pre-treatment, worms were surrounded by neutrophils, with eosinophils rare or absent. At 8-12weeks after either regimen, eosinophils increased around worms and were observed degranulating on the cuticle. However, with the SIR treatment, neutrophils returned to predominance by 48weeks, while in the COM group, eosinophilia persisted. These observations suggest that accumulation of degranulating eosinophils over a prolonged period is a cause rather than an effect of parasite death, and the macrofilaricidal mechanism of antibiotics may relate to facilitation of eosinophil infiltration around worms by ablation of Wolbachia-mediated neutrophilia.
Nfon
Charles K
CK
Liverpool School of Tropical Medicine and Faculty of Veterinary Science, University of Liverpool, Pembroke Place, Liverpool L3 5QA, UK.
Makepeace
Benjamin L
BL
Njongmeta
Leo M
LM
Tanya
Vincent N
VN
Bain
Odile
O
Trees
Alexander J
AJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002417:Cattle; D015550:Cell Degranulation; D004804:Eosinophils / Q000276:immunology*; D006651:Histocytochemistry; D007958:Leukocyte Count; D009854:Onchocerca / Q000276:immunology* / Q000382:microbiology*; D009855:Onchocerciasis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D010118:Oxytetracycline / Q000494:pharmacology* / Q000627:therapeutic use; D013559:Symbiosis; D020577:Wolbachia / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D010118:Oxytetracycline