Wolbachia surface protein (WSP) inhibits apoptosis in human neutrophils

Abstract

Polymorphonuclear cells (PMNs) are essential for the innate immune response against invading bacteria. At the same time, modulation of PMNs' apoptosis or cell death by bacteria has emerged as a mechanism of pathogenesis. Wolbachia bacteria are Gram-negative endosymbionts of filarial nematodes and arthropods, phylogenetically related to the genera Anaplasma, Ehrlichia and Neorickettsia (family Anaplasmataceae). Although several pathogens are known to interfere with apoptosis, there is only limited information on specific proteins that modulate this phenomenon. This is the first evidence for the anti-apoptotic activity of a surface protein of Wolbachia from filarial nematode parasites (the Wolbachia surface protein, WSP). The inhibition of apoptosis was demonstrated on purified human PMNs in vitro by different methods. TUNEL assay showed that the percentage of dead cells was reduced after stimulation with WSP; Annexin V-FITC binding assay confirmed that cell death was due mainly to apoptosis and not to necrosis. Reduced caspase-3 activity in stimulated cells also confirmed an inhibition of the apoptotic process.

Toll-Like Receptor 2 Regulates CXC Chemokine Production and Neutrophil Recruitment to the Cornea inOnchocerca volvulus/Wolbachia-Induced Keratitis

“…Brattig and colleagues reported that recombinant WSP activates dendritic cells and macrophages through TLR2 (6), and we reported that WSP is readily detected in the cornea after injection of microfilariae (16). Moreover, WSP induces IL-8 production in canine peripheral blood neutrophils (5) and also inhibits apoptosis of human neutrophils (4). Future studies will examine the role of WSP and other putative ligands in O. volvulus/Wolbachia-induced keratitis.…”

Genetic and Functional Characterization of the Type IV Secretion System inWolbachia

“…Two other wsp genes are present in the Wolbachia genome, of which one (wspA) is usually used in strain identification and phylogeny analyses (68), although currently these analyses are completed by multilocus sequence typing (3,4,47). The wsp locus encodes an outer surface protein (Wsp) whose homologue in Wolbachia strain wDm from the nematode Dirofilaria immitis is able to inhibit the apoptosis of human granulocytes (6). A gene for an antigenic outer membrane protein, a member of the p44 multigene family, is also cotranscribed with the virB-virD4 cluster in A. phagocytophilum (43).…”

Human and Animal Dirofilariasis: the Emergence of a Zoonotic Mosaic

“…Together with neutrophils, the key role of macrophages in the inflammation associated with onchocerciasis and lymphatic filariasis has been demonstrated (61,421). In this respect, some studies indicated that WSP induces the chemotaxis of neutrophils (37) and can inhibit their apoptosis in vitro, which could contribute to the extension of the inflammatory state (36). Moreover, the presence of Wolbachia or of its molecules in the cytoplasm of leukocytes of dogs and humans with cardiopulmonary or subcutaneous dirofilariasis has been shown by immunohistochemistry (162, 216) (see Fig.…”