A Cyanobacterial Lipopolysaccharide Antagonist Inhibits Cytokine Production Induced by Neisseria Meningitidis in a Human Whole-blood Model of Septicemia

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2008 Apr 30

PMID 18443097

Citations 9

Authors

Kim Jemmett

Annalisa Macagno

Monica Molteni

John E Heckels

Carlo Rossetti

Myron Christodoulides

Affiliations

Soon will be listed here.

Abstract

Septicemia caused by Neisseria meningitidis is characterized by increasing levels of meningococcal lipopolysaccharide (Nm-LPS) and cytokine production in the blood. We have used an in vitro human whole-blood model of meningococcal septicemia to investigate the potential of CyP, a selective Toll-like receptor 4 (TLR4)-MD-2 antagonist derived from the cyanobacterium Oscillatoria planktothrix FP1, for reducing LPS-mediated cytokine production. CyP (> or = 1 microg/ml) inhibited the secretion of the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-6 (by >90%) and chemokines IL-8 and monocyte chemoattractant protein 1 (by approximately 50%) induced by the treatment of blood with pure Nm-LPS, by isolated outer membranes, and after infection with live meningococci of different serogroups. In vitro studies with human dendritic cells and TLR4-transfected Jurkat cells demonstrated that CyP competitively inhibited Nm-LPS interactions with TLR4 and subsequent NF-kappaB activation. These data demonstrate that CyP is a potent antagonist of meningococcal LPS and could be considered a new adjunctive therapy for treating septicemia.

Citing Articles

MiR-146a induction by cyanobacterial lipopolysaccharide antagonist (CyP) mediates endotoxin cross-tolerance.

Molteni M, Bosi A, Saturni V, Rossetti C Sci Rep. 2018; 8(1):11367.

PMID: 30054544 PMC: 6063882. DOI: 10.1038/s41598-018-29820-w.

The Effect of Cyanobacterial LPS Antagonist (CyP) on Cytokines and Micro-RNA Expression Induced by LPS.

Molteni M, Bosi A, Rossetti C Toxins (Basel). 2018; 10(7).

PMID: 30012943 PMC: 6071223. DOI: 10.3390/toxins10070290.

Natural Products with Toll-Like Receptor 4 Antagonist Activity.

Molteni M, Bosi A, Rossetti C Int J Inflam. 2018; 2018:2859135.

PMID: 29686833 PMC: 5852877. DOI: 10.1155/2018/2859135.

Quantitative Simulations Predict Treatment Strategies Against Fungal Infections in Virtual Neutropenic Patients.

Timme S, Lehnert T, Prausse M, Hunniger K, Leonhardt I, Kurzai O Front Immunol. 2018; 9:667.

PMID: 29670632 PMC: 5893870. DOI: 10.3389/fimmu.2018.00667.

Effects of cyanobacteria Oscillatoria sp. lipopolysaccharide on B cell activation and Toll-like receptor 4 signaling.

Swanson-Mungerson M, Incrocci R, Subramaniam V, Williams P, Hall M, Mayer A Toxicol Lett. 2017; 275:101-107.

PMID: 28499610 PMC: 5510639. DOI: 10.1016/j.toxlet.2017.05.013.

References

Ialenti A, Di Meglio P, Grassia G, Maffia P, Di Rosa M, Lanzetta R . A novel lipid A from Halomonas magadiensis inhibits enteric LPS-induced human monocyte activation. Eur J Immunol. 2005; 36(2):354-60. DOI: 10.1002/eji.200535305. View

Gardlund B, Sjolin J, Nilsson A, Roll M, Wickerts C, Wretlind B . Plasma levels of cytokines in primary septic shock in humans: correlation with disease severity. J Infect Dis. 1995; 172(1):296-301. DOI: 10.1093/infdis/172.1.296. View

Lepper P, Triantafilou M, Schumann C, Schneider E, Triantafilou K . Lipopolysaccharides from Helicobacter pylori can act as antagonists for Toll-like receptor 4. Cell Microbiol. 2005; 7(4):519-28. DOI: 10.1111/j.1462-5822.2005.00482.x. View

Ison C . Whole-blood model. Methods Mol Med. 2011; 66:317-29. DOI: 10.1385/1-59259-148-5:317. View

Gonzalez-Rey E, Chorny A, Robledo G, Delgado M . Cortistatin, a new antiinflammatory peptide with therapeutic effect on lethal endotoxemia. J Exp Med. 2006; 203(3):563-71. PMC: 2118226. DOI: 10.1084/jem.20052017. View

Keleti G, Sykora J . Production and properties of cyanobacterial endotoxins. Appl Environ Microbiol. 1982; 43(1):104-9. PMC: 241788. DOI: 10.1128/aem.43.1.104-109.1982. View

Bhor V, Thomas C, Surolia N, Surolia A . Polymyxin B: an ode to an old antidote for endotoxic shock. Mol Biosyst. 2006; 1(3):213-22. DOI: 10.1039/b500756a. View

Medzhitov R, Preston-Hurlburt P, Janeway Jr C . A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997; 388(6640):394-7. DOI: 10.1038/41131. View

Levin M, Quint P, Goldstein B, Barton P, Bradley J, Shemie S . Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. rBPI21 Meningococcal Sepsis Study Group. Lancet. 2000; 356(9234):961-7. DOI: 10.1016/s0140-6736(00)02712-4. View

10.

Gheesling L, Carlone G, Pais L, Holder P, Maslanka S, Plikaytis B . Multicenter comparison of Neisseria meningitidis serogroup C anti-capsular polysaccharide antibody levels measured by a standardized enzyme-linked immunosorbent assay. J Clin Microbiol. 1994; 32(6):1475-82. PMC: 264022. DOI: 10.1128/jcm.32.6.1475-1482.1994. View

11.

Andra J, Gutsmann T, Garidel P, Brandenburg K . Mechanisms of endotoxin neutralization by synthetic cationic compounds. J Endotoxin Res. 2006; 12(5):261-77. DOI: 10.1179/096805106X118852. View

12.

Haziot A, Chen S, Ferrero E, Low M, Silber R, Goyert S . The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage. J Immunol. 1988; 141(2):547-52. View

13.

Kahler C, Stephens D . Genetic basis for biosynthesis, structure, and function of meningococcal lipooligosaccharide (endotoxin). Crit Rev Microbiol. 1999; 24(4):281-334. DOI: 10.1080/10408419891294216. View

14.

Sato K, Yoo Y, Fukushima A, Saiki I, Takahashi T, Fujihara M . A novel synthetic lipid A analog with low endotoxicity, DT-5461, prevents lethal endotoxemia. Infect Immun. 1995; 63(8):2859-66. PMC: 173388. DOI: 10.1128/iai.63.8.2859-2866.1995. View

15.

Macagno A, Molteni M, Rinaldi A, Bertoni F, Lanzavecchia A, Rossetti C . A cyanobacterial LPS antagonist prevents endotoxin shock and blocks sustained TLR4 stimulation required for cytokine expression. J Exp Med. 2006; 203(6):1481-92. PMC: 2118317. DOI: 10.1084/jem.20060136. View

16.

Stephens D, Greenwood B, Brandtzaeg P . Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet. 2007; 369(9580):2196-2210. DOI: 10.1016/S0140-6736(07)61016-2. View

17.

Brandtzaeg P, Bjerre A, Ovstebo R, Brusletto B, Joo G, Kierulf P . Neisseria meningitidis lipopolysaccharides in human pathology. J Endotoxin Res. 2001; 7(6):401-20. View

18.

Waage A, Halstensen A, Espevik T, Brandtzaeg P . Compartmentalization of TNF and IL-6 in meningitis and septic shock. Mediators Inflamm. 1993; 2(1):23-5. PMC: 2365385. DOI: 10.1155/S096293519300002X. View

19.

McGuinness B, Clarke I, Lambden P, Barlow A, Poolman J, Jones D . Point mutation in meningococcal por A gene associated with increased endemic disease. Lancet. 1991; 337(8740):514-7. DOI: 10.1016/0140-6736(91)91297-8. View

20.

ZAK K, Diaz J, Jackson D, Heckels J . Antigenic variation during infection with Neisseria gonorrhoeae: detection of antibodies to surface proteins in sera of patients with gonorrhea. J Infect Dis. 1984; 149(2):166-74. DOI: 10.1093/infdis/149.2.166. View