Human filarial Wolbachia lipopeptide directly activates human neutrophils in vitro.

Tamarozzi, Francesca, Wright, Helen L, Johnston, Kelly, Edwards, Steven W, Turner, Joseph ORCID: https://orcid.org/0000-0002-2185-5476 and Taylor, Mark ORCID: https://orcid.org/0000-0003-3396-9275 (2014) 'Human filarial Wolbachia lipopeptide directly activates human neutrophils in vitro.'. Parasite Immunology, Vol 36, Issue 10, pp. 494-502.

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Abstract

The host inflammatory response to the Onchocerca volvulus endosymbiont, Wolbachia, 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 Wolbachia, membrane-associated diacylated lipoproteins, were 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 Wolbachia pattern recognition motif is not known. Therefore, the responses of purified peripheral blood human neutrophils to a synthetic N-terminal diacylated lipopeptide (WoLP) of filarial Wolbachia peptidoglycan-associated lipoprotein (PAL) were characterised. WoLP 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. WoLP exposure induced chemotaxis but not chemokinesis of neutrophils, and secretion of the major neutrophil chemokine, interleukin 8. WoLP 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 Wolbachia lipoproteins directly activates human neutrophils in vitro and promotes a molecular pathway by which human neutrophils are recruited to sites of Onchocerca parasitism.

Item Type:	Article
Subjects:	QU Biochemistry > Carbohydrates. Lipids > QU 85 Lipids QX Parasitology > Helminths. Annelida > QX 301 Filarioidea QX Parasitology > QX 45 Host-parasite relations WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General)
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1111/pim.12122
Depositing User:	Mary Creegan
Date Deposited:	29 Aug 2014 10:52
Last Modified:	16 Sep 2019 09:01
URI:	https://archive.lstmed.ac.uk/id/eprint/3828

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