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Published on: May 12, 2023
Wolbachia surface protein (WSP) inhibits apoptosis in human neutrophils
C Bazzocchi1, S Comazzi, R Santoni
1Dipartimento di Patologia Animale Igiene e Sanità Pubblica Veterinaria, Sezione di Patologia Generale e Parassitologia, Università di Milano, Milano, Italy.
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.
Insights
The Wolbachia surface protein (WSP) inhibits programmed cell death in human immune cells. This discovery sheds light on bacterial pathogenesis and immune evasion strategies employed by Wolbachia.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Polymorphonuclear cells (PMNs) are critical for innate immunity against bacterial infections.
- Bacterial manipulation of PMN apoptosis is a key pathogenic mechanism.
- Wolbachia bacteria, endosymbionts of filarial nematodes, are phylogenetically linked to Anaplasmataceae.
Purpose of the Study:
- To investigate the role of Wolbachia surface protein (WSP) in modulating human PMN apoptosis.
- To provide the first evidence of anti-apoptotic activity by a Wolbachia surface protein.
Main Methods:
- Purified human PMNs were stimulated with WSP in vitro.
- TUNEL assay was used to quantify cell death.
- Annexin V-FITC binding assay differentiated apoptosis from necrosis.
- Caspase-3 activity was measured to confirm apoptosis inhibition.
Main Results:
- WSP stimulation significantly reduced the percentage of dead cells in human PMNs.
- Annexin V-FITC assays indicated that cell death was primarily apoptotic.
- Caspase-3 activity was reduced in WSP-stimulated cells, confirming apoptosis inhibition.
Conclusions:
- The Wolbachia surface protein (WSP) exhibits anti-apoptotic activity on human PMNs.
- WSP may represent a novel mechanism for bacterial immune evasion.
- This finding contributes to understanding the pathogenesis of Wolbachia-associated infections.
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