Activation of human monocytes by live Borrelia burgdorferi generates TLR2-dependent and -independent responses which include induction of IFN-beta

PLoS Pathogens
Juan C SalazarJustin D Radolf

Abstract

It is widely believed that innate immune responses to Borrelia burgdorferi (Bb) are primarily triggered by the spirochete's outer membrane lipoproteins signaling through cell surface TLR1/2. We recently challenged this notion by demonstrating that phagocytosis of live Bb by peripheral blood mononuclear cells (PBMCs) elicited greater production of proinflammatory cytokines than did equivalent bacterial lysates. Using whole genome microarrays, we show herein that, compared to lysates, live spirochetes elicited a more intense and much broader transcriptional response involving genes associated with diverse cellular processes; among these were IFN-beta and a number of interferon-stimulated genes (ISGs), which are not known to result from TLR2 signaling. Using isolated monocytes, we demonstrated that cell activation signals elicited by live Bb result from cell surface interactions and uptake and degradation of organisms within phagosomes. As with PBCMs, live Bb induced markedly greater transcription and secretion of TNF-alpha, IL-6, IL-10 and IL-1beta in monocytes than did lysates. Secreted IL-18, which, like IL-1beta, also requires cleavage by activated caspase-1, was generated only in response to live Bb. Pro-inflammatory cytokine...Continue Reading

References

Oct 1, 1992·Infection and Immunity·M G RittigG R Burmester
Apr 1, 1990·Infection and Immunity·M E BrandtM V Norgard
Sep 1, 1987·Infection and Immunity·K TakayamaA G Barbour
Nov 1, 1984·The Journal of Infectious Diseases·J L BenachG S Habicht
Oct 1, 1994·The Journal of Infectious Diseases·R R MontgomeryS E Malawista
Apr 1, 1994·Current Opinion in Pediatrics·A WalkerM E Wilson
Jul 1, 1994·Journal of Neurosurgery·G B WellsE L Zager
Jul 1, 1996·Infection and Immunity·R R Montgomery, S E Malawista
Jul 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·D L CoxJ D Radolf
Jun 11, 1999·The Journal of Biological Chemistry·R SchwandnerC J Kirschning
Aug 31, 1999·Immunopharmacology and Immunotoxicology·R MarzioS Betz-Corradin
Nov 24, 1999·The Journal of Biological Chemistry·E LienD T Golenbock
Feb 19, 2000·Current Opinion in Immunology·S Akira
Nov 30, 2000·Proceedings of the National Academy of Sciences of the United States of America·A OzinskyA Aderem
Mar 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·T J SellatiJ D Radolf
Apr 6, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·R J BinderP K Srivastava
Aug 22, 2001·The Journal of Biological Chemistry·D W LaFleurP A Moore
Dec 26, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·R Mark WootenJanis J Weis
Jan 15, 2002·The Journal of Biological Chemistry·Michael P MalakhovDong-Er Zhang
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen

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Citations

Jul 10, 2010·Journal of Leukocyte Biology·Marco A Quevedo-DiazAndrei E Medvedev
Feb 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jorge L CervantesJuan C Salazar
Jan 11, 2012·Proceedings of the National Academy of Sciences of the United States of America·Kelly L HawleyJuan Anguita
Jan 11, 2013·The Journal of Infectious Diseases·Justin D Radolf
Jan 26, 2013·PloS One·Stephan DreschersThorsten W Orlikowsky
Jan 22, 2013·Cell Communication and Signaling : CCS·Karla Lh FeijsBernhard Lüscher
Mar 1, 2012·Current Colorectal Cancer Reports·Rong LuJun Sun
Aug 23, 2016·Current Tropical Medicine Reports·Dana K ShawJoao H F Pedra
Jun 26, 2014·Critical Reviews in Microbiology·Marije OostingLeo A B Joosten
May 16, 2015·Parasites & Vectors·Jaroslava LieskovskáJan Kopecký
Jan 7, 2014·Trends in Parasitology·Lauren M K MasonJoppe W R Hovius
Jan 8, 2015·Frontiers in Cellular and Infection Microbiology·Tanja Petnicki-Ocwieja, Aurelie Kern
Jun 27, 2014·Frontiers in Cellular and Infection Microbiology·Alexia A BelperronLinda K Bockenstedt
Dec 16, 2016·Nature Reviews. Disease Primers·Allen C SteerePaul S Mead
Oct 8, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jackie K PaquetteJanis J Weis
Apr 12, 2013·Nature Communications·Patricia VerheugdBernhard Lüscher
Oct 23, 2012·Cellular & Molecular Immunology·Jorge L CervantesJuan C Salazar
Feb 1, 2011·Cellular & Molecular Immunology·Amy D ProalTrevor G Marshall
Nov 21, 2012·Infection and Immunity·Tanja Petnicki-OcwiejaLinden T Hu
Nov 5, 2016·PloS One·Raphaële ThiébautVincent Ollendorff
Mar 8, 2018·Emerging Microbes & Infections·Ana Carreras-GonzálezJuan Anguita
Jan 12, 2010·American Journal of Reproductive Immunology : AJRI·Erik NormannLarry J Guilbert
Apr 9, 2010·Current Opinion in Rheumatology·Bettina Panagiota Iliopoulou, Brigitte T Huber
May 21, 2010·Cellular Microbiology·Kathryn M MonroeRussell E Vance

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Methods Mentioned

BETA
Ubiquitination
PCR
flow cytometry
ELISA
confocal microscopy
flow
density gradient centrifugation
fluorescence-activated
FACS
lavage

Software Mentioned

R language
Beadstudio
LSM Image Browser
Bioconductor
Chip
GraphPad Prism
WinMDI
MAANOVA
ImageJ
R

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