Human filarial Wolbachia lipopeptide directly activates human neutrophils in vitro. (October 2014)

• Record Type: Journal Article
• Authors: Tamarozzi, F.; Wright, H. L.; Johnston, K. L.; Edwards, S. W.; Turner, J. D.; Taylor, M. J.
• Is Part Of: Parasite immunology. Volume 36:Number 10(2014:Oct.)
• Page Start: 494
• Page End: 502
• Publication Date: 2014-10
• Subjects: Veterinary parasitology -- Immunological aspects -- Periodicals; Host-parasite relationships -- Immunological aspects -- Periodicals; 571.96
• DOI: 10.1111/pim.12122
• Languages: English
• ISSNs: 0141-9838

Abstract

<abstract abstract-type="main" id="pim12122-abs-0001"> <title>Summary</title> <p>The host inflammatory response to the <italic>Onchocerca volvulus</italic> endosymbiont, <italic>Wolbachia</italic>, is a major contributing factor in the development of chronic pathology in humans (onchocerciasis/river blindness). Recently, the toll‐like pattern recognition receptor motif of the major inflammatory ligands of filarial <italic>Wolbachia</italic>, membrane‐associated diacylated lipoproteins, was functionally defined in murine models of pathology, including mediation of neutrophil recruitment to the cornea. However, the extent to which human neutrophils can be activated in response to this <italic>Wolbachia</italic> pattern recognition motif is not known. Therefore, the responses of purified peripheral blood human neutrophils to a synthetic N‐terminal diacylated lipopeptide (<italic>Wo</italic>LP) of filarial <italic>Wolbachia</italic> peptidoglycan‐associated lipoprotein (PAL) were characterized. <italic>Wo</italic>LP exposure led to a dose‐dependent activation of healthy, human neutrophils that included gross morphological alterations and modulation of surface expressed integrins involved in tethering, rolling and extravasation. <italic>Wo</italic>LP exposure induced chemotaxis but not chemokinesis of neutrophils, and secretion of the major neutrophil chemokine, interleukin 8. <italic>Wo</italic>LP also induced and primed the respiratory burst, and enhanced neutrophil survival by delay of apoptosis. These results indicate that the major inflammatory motif of filarial <italic>Wolbachia</italic> lipoproteins directly activates human neutrophils <italic>in vitro</italic> and promotes a molecular pathway by which human neutrophils are recruited to sites of <italic>Onchocerca</italic> parasitism.</p> </abstract>