Proteomic analysis of cholera toxin adjuvant-stimulated human monocytes identifies Thrombospondin-1 and Integrin-β1 as strongly upregulated molecules involved in adjuvant activity

Scientific Reports
Manuela TerrinoniMaximilian Larena

Abstract

Cholera Toxin (CT) as well as its related non-toxic mmCT and dmLT mutant proteins have been shown to be potent adjuvants for mucosally administered vaccines. Their adjuvant activity involves activation of cAMP/protein kinase A (PKA) signaling and inflammasome/IL-1β pathways in antigen presenting cells (APC). To get a further understanding of the signal transduction and downstream pathways activated in APCs by this group of adjuvants we have, employing quantitative proteomic analytic tools, investigated human monocytes at various time points after treatment with CT. We report the activation of three main biological pathways among upregulated proteins, peaking at 16 hours of CT treatment: cellular organization, metabolism, and immune response. Specifically, in the further analyzed immune response pathway we note a strong upregulation of thrombospondin 1 (THBS1) and integrin β1 (ITGB1) in response to CT as well as to mmCT and dmLT, mediated via cAMP/PKA and NFKB signaling. Importantly, inhibition in vitro of THSB1 and ITGB1 in monocytes or primary dendritic cells using siRNA abrogated the ability of the treated APCs to promote an adjuvant-stimulated Th17 cell response when co-cultured with peripheral blood lymphocytes indicating t...Continue Reading

References

Aug 14, 1999·Science·F G Giancotti, E Ruoslahti
Aug 15, 2000·European Journal of Immunology·M C GagliardiM T De Magistris
Dec 5, 2000·Matrix Biology : Journal of the International Society for Matrix Biology·H ChenJ Lawler
Aug 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ed C LavelleKingston H G Mills
Aug 5, 2004·The Journal of Biological Chemistry·Maria J CalzadaDavid D Roberts
Sep 29, 2007·Nature Methods·Thomas Köcher, Giulio Superti-Furga
Jul 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·F MoscaE De Gregorio
Sep 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Matthias Mann, Neil L Kelleher
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Feb 16, 2010·Immunity·Diana M Mitchell, Matthew A Williams
May 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sandip K DattaEyal Raz
Feb 4, 2011·Clinical and Vaccine Immunology : CVI·Elizabeth B NortonJohn D Clements
Jul 19, 2011·Mediators of Inflammation·Zenaida Lopez-DeeLinda S Gutierrez
Feb 22, 2012·Journal of Cell Science·Mónica Sala-ValdésMaría Yáñez-Mó
Apr 3, 2012·Expert Review of Proteomics·Feng YangRichard D Smith
Dec 4, 2012·Nucleic Acids Research·Juan Antonio VizcaínoHenning Hermjakob
Jul 23, 2013·Nature Protocols·Huaiyu MiPaul D Thomas
Sep 13, 2013·Journal of Proteome Research·Oliver SerangJudith A Steen
Jan 31, 2014·Matrix Biology : Journal of the International Society for Matrix Biology·Andrea ResoviGiulia Taraboletti
Oct 23, 2014·Journal of Proteome Research·Tanveer S BatthJesper V Olsen
Dec 4, 2014·Analytica Chimica Acta·Julie A Stenken, Andreas J Poschenrieder
Dec 24, 2014·Nature Reviews. Immunology·Edward J Pearce, Bart Everts
Mar 20, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maximilian LarenaAnna Lundgren
May 20, 2015·Vaccine·Thorunn OlafsdottirAli M Harandi
Mar 5, 2016·Molecular & Cellular Proteomics : MCP·Djin-Ye OhOfer Levy
Mar 18, 2017·Lancet·John D ClemensJan Holmgren

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Citations

Apr 3, 2020·Pathogens·Konstantin IvanovSvetlana Khaiboullina
May 21, 2020·Frontiers in Microbiology·Yeongjun BaekEun Jin Kim
Aug 20, 2019·Current Medicinal Chemistry·Thaise Gonçalves AraújoAdemar Alves da Silva Filho

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Methods Mentioned

BETA
ELISA
density-gradient centrifugation
protein assay
Transfection
flow cytometry

Software Mentioned

FlowJo
Tree Star
Proteome Discoverer
All
DAVID
PANTHER
Proteome Discover

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