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A Novel Ligand of Toll-like Receptor 4 From the Sheath of Wuchereria bancrofti Microfilaria Induces Proinflammatory Response in Macrophages.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2017 Mar 15; Vol. 215 (6), pp. 954-965. - Publication Year :
- 2017
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Abstract
- Background: Lymphatic filariasis, frequently caused from Wuchereria bancrofti infection, is endemic in several parts of the globe and responsible for human health problems and socioeconomic loss to a large extent. Inflammatory consequences originating from host-parasite interaction play a major role in the disease pathology and allied complications. The identity of the key mediator of this process is yet unknown in filarial research.<br />Methods: Microfilarial protein (MfP) was isolated from the sheath of W. bancrofti microfilariae through ultrafiltration, followed by chromatographic separation. Expression of signaling molecules was studied by enzyme-linked immunosorbent assay and immunoblotting. Binding of MfP to Toll-like receptor 4 (TLR4) was determined by co-immunoprecipitation, fluorescein isothiocyanate-probing, and surface plasmon resonance analysis.<br />Results: We found that MfP (approximately 70 kDa) binds to macrophage-TLR4 and triggers nuclear factor kappa beta activation that upregulates secretion of proinflammatory cytokines. Microfilarial protein failed to induce inflammation in either TLRKO macrophage or macrophage treated with TLR4 inhibitor, indicating that MfP acts through TLR4. We have also detected phenotypic transformation of macrophages from anti-inflammatory (M2) to proinflammatory (M1) subtype after incubation with MfP.<br />Conclusions: Microfilarial protein appears to be a new ligand of TLR4 from W. bancrofti. Determination of its functional attributions in the host-parasite relationship, especially immunopathogenesis of filarial infection, may improve our understanding.<br /> (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Subjects :
- Animals
Antibodies, Helminth blood
Cells, Cultured
Enzyme-Linked Immunosorbent Assay
HEK293 Cells
Host-Parasite Interactions
Humans
Ligands
Mice
Mice, Inbred BALB C
Microfilariae immunology
Antigens, Helminth immunology
Helminth Proteins immunology
Macrophages immunology
Toll-Like Receptor 4 immunology
Wuchereria bancrofti immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6613
- Volume :
- 215
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 28453850
- Full Text :
- https://doi.org/10.1093/infdis/jix067