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The endosymbiotic bacteria,  Wolbachia,  induce neutrophilic responses to the human helminth pathogen  Onchocerca volvulus.  The formation of Neutrophil Extracellular Traps (NETs), has been implicated in anti-microbial defence, but has not been identified in human helminth infection. Here, we demonstrate NETs formation in human onchocerciasis. Extracellular NETs and neutrophils were visualised around  O. volvulus  in nodules excised from untreated patients but not in nodules from patients treated with the anti- Wolbachia  drug, doxycycline. Whole  Wolbachia  or microspheres coated with a synthetic  Wolbachia  lipopeptide ( Wo LP) of the major nematode  Wolbachia  TLR2/6 ligand, peptidoglycan associated lipoprotein, induced NETosis in human neutrophils  in vitro . TLR6 dependency of  Wolbachia  and  Wo LP NETosis was demonstrated using purified neutrophils from TLR6 deficient mice. Thus, we demonstrate for the first time that NETosis occurs during natural human helminth infection and demonstrate a mechanism of NETosis induction via  Wolbachia  endobacteria and direct ligation of  Wolbachia  lipoprotein by neutrophil TLR2/6.

Wolbachia endosymbionts induce neutrophil extracellular trap formation in human onchocerciasis