Premium
Human filarial Wolbachia lipopeptide directly activates human neutrophils in vitro
Author(s) -
Tamarozzi F.,
Wright H. L.,
Johnston K. L.,
Edwards S. W.,
Turner J. D.,
Taylor M. J.
Publication year - 2014
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1111/pim.12122
Subject(s) - biology , wolbachia , onchocerca volvulus , immunology , chemotaxis , chemokine , neutrophil extracellular traps , microbiology and biotechnology , inflammation , receptor , onchocerciasis , gene , biochemistry
Summary 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, 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 Wolbachia pattern recognition motif is not known. Therefore, the responses of purified peripheral blood human neutrophils to a synthetic N‐terminal diacylated lipopeptide ( Wo LP) of filarial Wolbachia peptidoglycan‐associated lipoprotein (PAL) were characterized. Wo 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. Wo LP exposure induced chemotaxis but not chemokinesis of neutrophils, and secretion of the major neutrophil chemokine, interleukin 8. Wo 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 Wolbachia lipoproteins directly activates human neutrophils in vitro and promotes a molecular pathway by which human neutrophils are recruited to sites of Onchocerca parasitism.