Ver registro no DEDALUS
Exportar registro bibliográfico



CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition (2017)

  • Authors:
  • USP Schools: FMRP
  • DOI: 10.1038/s41598-017-07397-0
  • Agências de fomento:
  • Language: Inglês
  • Imprenta:
  • Source:
  • Acesso online ao documento

    Online accessDOI or search this record in
    Informações sobre o DOI: 10.1038/s41598-017-07397-0 (Fonte: oaDOI API)
    • Este periódico é de acesso aberto
    • Este artigo é de acesso aberto
    • URL de acesso aberto
    • Cor do Acesso Aberto: bronze
    • Licença: cc-by

    How to cite
    A citação é gerada automaticamente e pode não estar totalmente de acordo com as normas

    • ABNT

      SILVA, Thiago Aparecido da; ZORZETTO-FERNANDES, André L. V.; CECÍLIO, Nerry T.; et al. CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition. Scientific Reports, London, v. 7, n. 1, 2017. Disponível em: < > DOI: 10.1038/s41598-017-07397-0.
    • APA

      Silva, T. A. da, Zorzetto-Fernandes, A. L. V., Cecílio, N. T., Sardinha-Silva, A., Fernandes, F. F., & Roque-Barreira, M. C. (2017). CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition. Scientific Reports, 7( 1). doi:10.1038/s41598-017-07397-0
    • NLM

      Silva TA da, Zorzetto-Fernandes ALV, Cecílio NT, Sardinha-Silva A, Fernandes FF, Roque-Barreira MC. CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition [Internet]. Scientific Reports. 2017 ; 7( 1):Available from:
    • Vancouver

      Silva TA da, Zorzetto-Fernandes ALV, Cecílio NT, Sardinha-Silva A, Fernandes FF, Roque-Barreira MC. CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition [Internet]. Scientific Reports. 2017 ; 7( 1):Available from:

    Referências citadas na obra
    Robbins, J. B., Schneerson, R. & Szu, S. C. Perspective: hypothesis: serum IgG antibody is sufficient to confer protection against infectious diseases by inactivating the inoculum. J Infect Dis 171, 1387–1398 (1995).
    Griffiths, K. L. & Khader, S. A. Novel vaccine approaches for protection against intracellular pathogens. Curr Opin Immunol 28, 58–63, doi: 10.1016/j.coi.2014.02.003 (2014).
    Dasgupta, S., Aghazadeh-Dibavar, S. & Bandyopadyay, M. The role of toll-like receptor agonists in the immunotherapy of leishmaniosis. An update and proposal for a new form of anti-leishmanial therapy. Ann Parasitol 60, 75–82 (2014).
    Cluff, C. W. et al. Synthetic toll-like receptor 4 agonists stimulate innate resistance to infectious challenge. Infect Immun 73, 3044–3052, doi: 10.1128/IAI.73.5.3044-3052.2005 (2005).
    Zhang, W. W. & Matlashewski, G. Immunization with a Toll-like receptor 7 and/or 8 agonist vaccine adjuvant increases protective immunity against Leishmania major in BALB/c mice. Infect Immun 76, 3777–3783, doi: 10.1128/IAI.01527-07 (2008).
    Huang, L., Hinchman, M. & Mendez, S. Coinjection with TLR2 agonist Pam3CSK4 reduces the pathology of leishmanization in mice. PLoS Negl Trop Dis 9, e0003546, doi: 10.1371/journal.pntd.0003546 (2015).
    O’Neill, L. A. & Bowie, A. G. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol 7, 353–364, doi: 10.1038/nri2079 (2007).
    Chattopadhyay, S. & Sen, G. C. Tyrosine phosphorylation in Toll-like receptor signaling. Cytokine Growth Factor Rev 25, 533–541, doi: 10.1016/j.cytogfr.2014.06.002 (2014).
    Kagan, J. C., Magupalli, V. G. & Wu, H. SMOCs: supramolecular organizing centres that control innate immunity. Nat Rev Immunol 14, 821–826, doi: 10.1038/nri3757 (2014).
    Rosadini, C. V. & Kagan, J. C. Microbial strategies for antagonizing Toll-like-receptor signal transduction. Curr Opin Immunol 32, 61–70, doi: 10.1016/j.coi.2014.12.011 (2015).
    Pandey, S., Kawai, T. & Akira, S. Microbial Sensing by Toll-Like Receptors and Intracellular Nucleic Acid Sensors. Cold Spring Harb Perspect Biol. 7, a016246 (2015).
    Brightbill, H. D. et al. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285, 732–736 (1999).
    Zhu, X., Ramos, T. V., Gras-Masse, H., Kaplan, B. E. & BenMohamed, L. Lipopeptide epitopes extended by an Nepsilon-palmitoyl-lysine moiety increase uptake and maturation of dendritic cells through a Toll-like receptor-2 pathway and trigger a Th1-dependent protective immunity. Eur J Immunol 34, 3102–3114, doi: 10.1002/eji.200425166 (2004).
    Cote-Sierra, J. et al. Bacterial lipoprotein-based vaccines induce tumor necrosis factor-dependent type 1 protective immunity against Leishmania major. Infect Immun 70, 240–248 (2002).
    Sieling, P. A., Chung, W., Duong, B. T., Godowski, P. J. & Modlin, R. L. Toll-like receptor 2 ligands as adjuvants for human Th1 responses. J Immunol 170, 194–200 (2003).
    Imanishi, T. et al. Cutting edge: TLR2 directly triggers Th1 effector functions. J Immunol 178, 6715–6719 (2007).
    van Bergenhenegouwen, J. et al. TLR2 & Co: a critical analysis of the complex interactions between TLR2 and coreceptors. J Leukoc Biol 94, 885–902, doi: 10.1189/jlb.0113003 (2013).
    Kelley, S. L., Lukk, T., Nair, S. K. & Tapping, R. I. The crystal structure of human soluble CD14 reveals a bent solenoid with a hydrophobic amino-terminal pocket. J Immunol 190, 1304–1311, doi: 10.4049/jimmunol.1202446 (2013).
    Meng, J., Parroche, P., Golenbock, D. T. & McKnight, C. J. The differential impact of disulfide bonds and N-linked glycosylation on the stability and function of CD14. J Biol Chem 283, 3376–3384, doi: 10.1074/jbc.M707640200 (2008).
    Jin, M. S. et al. Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell 130, 1071–1082, doi: 10.1016/j.cell.2007.09.008 (2007).
    Iwasaki, A. & Medzhitov, R. Toll-like receptor control of the adaptive immune responses. Nat Immunol 5, 987–995, doi: 10.1038/ni1112 (2004).
    Dunne, A., Marshall, N. A. & Mills, K. H. TLR based therapeutics. Curr Opin Pharmacol 11, 404–411, doi: 10.1016/j.coph.2011.03.004 (2011).
    Junquera, E. C., Mateos-Hernandez, L., de la Fuente, J. & de la Lastra, J. M. Recent advances in the development of anti-infective prophylactic and/or therapeutic agents based on Toll-Like Receptor (TLRs). Recent Pat Antiinfect Drug Discov 9, 14–24 (2014).
    Santos-de-Oliveira, R., Dias-Baruffi, M., Thomaz, S. M., Beltramini, L. M. & Roque-Barreira, M. C. A neutrophil migration-inducing lectin from Artocarpus integrifolia. J Immunol 153, 1798–1807 (1994).
    Panunto-Castelo, A., Souza, M. A., Roque-Barreira, M. C. & Silva, J. S. KM(+), a lectin from Artocarpus integrifolia, induces IL-12 p40 production by macrophages and switches from type 2 to type 1 cell-mediated immunity against Leishmania major antigens, resulting in BALB/c mice resistance to infection. Glycobiology 11, 1035–1042 (2001).
    Teixeira, C. R. et al. Potential of KM+ lectin in immunization against Leishmania amazonensis infection. Vaccine 24, 3001–3008, doi: 10.1016/j.vaccine.2005.11.067 (2006).
    Coltri, K. C. et al. Therapeutic administration of KM+ lectin protects mice against Paracoccidioides brasiliensis infection via interleukin-12 production in a toll-like receptor 2-dependent mechanism. Am J Pathol 173, 423–432, doi: 10.2353/ajpath.2008.080126 (2008).
    Coltri, K. C. et al. Protection against Paracoccidioides brasiliensis infection conferred by the prophylactic administration of native and recombinant ArtinM. Med Mycol 48, 792–799, doi: 10.3109/13693780903501671 (2010).
    Cardoso, M. R. et al. ArtinM, a D-mannose-binding lectin from Artocarpus integrifolia, plays a potent adjuvant and immunostimulatory role in immunization against Neospora caninum. Vaccine 29, 9183–9193, doi: 10.1016/j.vaccine.2011.09.136 (2011).
    Custodio, L. A., Loyola, W., Conchon-Costa, I., da Silva Quirino, G. F. & Felipe, I. Protective effect of Artin M from extract of Artocarpus integrifolia seeds by Th1 and Th17 immune response on the course of infection by Candida albicans. Int Immunopharmacol 11, 1510–1515, doi: 10.1016/j.intimp.2011.05.005 (2011).
    Mariano, V. S. et al. Recognition of TLR2 N-glycans: critical role in ArtinM immunomodulatory activity. PLoS One 9, e98512, doi: 10.1371/journal.pone.0098512 (2014).
    Cecilio, N. T. et al. Yeast expressed ArtinM shares structure, carbohydrate recognition, and biological effects with native ArtinM. Int J Biol Macromol 82, 22–30, doi: 10.1016/j.ijbiomac.2015.09.062 (2016).
    Liu, Y., Cecilio, N. T., Carvalho, F. C., Roque-Barreira, M. C. & Feizi, T. Glycan microarray analysis of the carbohydrate-recognition specificity of native and recombinant forms of the lectin ArtinM. Data Brief 5, 1035–1047, doi: 10.1016/j.dib.2015.11.014 (2015).
    Alegre, A. C., Oliveira, A. F., Dos Reis Almeida, F. B., Roque-Barreira, M. C. & Hanna, E. S. Recombinant paracoccin reproduces the biological properties of the native protein and induces protective Th1 immunity against Paracoccidioides brasiliensis infection. PLoS Negl Trop Dis 8, e2788, doi: 10.1371/journal.pntd.0002788 (2014).
    Alegre-Maller, A. C. et al. Therapeutic administration of recombinant Paracoccin confers protection against paracoccidioides brasiliensis infection: involvement of TLRs. PLoS Negl Trop Dis 8, e3317, doi: 10.1371/journal.pntd.0003317 (2014).
    Pinzan, C. F. et al. Vaccination with Recombinant Microneme Proteins Confers Protection against Experimental Toxoplasmosis in Mice. PLoS One 10, e0143087, doi: 10.1371/journal.pone.0143087 (2015).
    Walker, D. B., Joshi, G. & Davis, A. P. Progress in biomimetic carbohydrate recognition. Cell Mol Life Sci 66, 3177–3191, doi: 10.1007/s00018-009-0081-8 (2009).
    Edwards, J. P., Zhang, X., Frauwirth, K. A. & Mosser, D. M. Biochemical and functional characterization of three activated macrophage populations. J Leukoc Biol 80, 1298–1307, doi: 10.1189/jlb.0406249 (2006).
    Toledo, K. A. et al. Neutrophil activation induced by ArtinM: release of inflammatory mediators and enhancement of effector functions. Immunol Lett 123, 14–20, doi: 10.1016/j.imlet.2009.01.009 (2009).
    da Silva, T. A., Roque-Barreira, M. C., Casadevall, A. & Almeida, F. Extracellular vesicles from Paracoccidioides brasiliensis induced M1 polarization in vitro. Sci Rep 6, 35867, doi: 10.1038/srep35867 (2016).
    Wang, C. et al. Characterization of murine macrophages from bone marrow, spleen and peritoneum. BMC Immunol 14, 6, doi: 10.1186/1471-2172-14-6 (2013).
    Huang, B. et al. Gr-1+ CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res 66, 1123–1131, doi: 10.1158/0008-5472.CAN-05-1299 (2006).
    Andreesen, R. et al. Surface phenotype analysis of human monocyte to macrophage maturation. J Leukoc Biol 47, 490–497 (1990).
    Wang, Y. et al. A critical role of activin A in maturation of mouse peritoneal macrophages in vitro and in vivo. Cell Mol Immunol 6, 387–392, doi: 10.1038/cmi.2009.50 (2009).
    Warren, M. K. & Vogel, S. N. Bone marrow-derived macrophages: development and regulation of differentiation markers by colony-stimulating factor and interferons. J Immunol 134, 982–989 (1985).
    Xu, W. et al. Human peritoneal macrophages show functional characteristics of M-CSF-driven anti-inflammatory type 2 macrophages. Eur J Immunol 37, 1594–1599, doi: 10.1002/eji.200737042 (2007).
    Manukyan, M. et al. Binding of lipopeptide to CD14 induces physical proximity of CD14, TLR2 and TLR1. Eur J Immunol 35, 911–921, doi: 10.1002/eji.200425336 (2005).
    Gangloff, S. C. et al. Influence of CD14 on ligand interactions between lipopolysaccharide and its receptor complex. J Immunol 175, 3940–3945 (2005).
    Park, O. J. et al. Lipoteichoic acid of Enterococcus faecalis induces the expression of chemokines via TLR2 and PAFR signaling pathways. J Leukoc Biol 94, 1275–1284, doi: 10.1189/jlb.1012522 (2013).
    Hattor, Y., Kasai, K., Akimoto, K. & Thiemermann, C. Induction of NO synthesis by lipoteichoic acid from Staphylococcus aureus in J774 macrophages: involvement of a CD14-dependent pathway. Biochem Biophys Res Commun 233, 375–379, doi: 10.1006/bbrc.1997.6462 (1997).
    Dessing, M. C. et al. Role played by Toll-like receptors 2 and 4 in lipoteichoic acid-induced lung inflammation and coagulation. J Infect Dis 197, 245–252, doi: 10.1086/524873 (2008).
    Jeon, J. H. et al. The Poly-gamma-d-Glutamic Acid Capsule Surrogate of the Bacillus anthracis Capsule Is a Novel Toll-Like Receptor 2 Agonist. Infect Immun 83, 3847–3856, doi: 10.1128/IAI.00888-15 (2015).
    Gangloff, S. C., Hijiya, N., Haziot, A. & Goyert, S. M. Lipopolysaccharide structure influences the macrophage response via CD14-independent and CD14-dependent pathways. Clin Infect Dis 28, 491–496, doi: 10.1086/515176 (1999).
    Carvalho, F. C., Soares, S. G., Tamarozzi, M. B., Rego, E. M. & Roque-Barreira, M. C. The recognition of N-glycans by the lectin ArtinM mediates cell death of a human myeloid leukemia cell line. PLoS One 6, e27892, doi: 10.1371/journal.pone.0027892 (2011).
    Hong, S. W. et al. Lipoteichoic acid of Streptococcus mutans interacts with Toll-like receptor 2 through the lipid moiety for induction of inflammatory mediators in murine macrophages. Mol Immunol 57, 284–291, doi: 10.1016/j.molimm.2013.10.004 (2014).
    Matsuguchi, T. et al. Lipoteichoic acids from Lactobacillus strains elicit strong tumor necrosis factor alpha-inducing activities in macrophages through Toll-like receptor 2. Clin Diagn Lab Immunol 10, 259–266 (2003).
    Cao, S. et al. Differential regulation of IL-12 and IL-10 gene expression in macrophages by the basic leucine zipper transcription factor c-Maf fibrosarcoma. J Immunol 169, 5715–5725 (2002).
    Maa, M. C. et al. The iNOS/Src/FAK axis is critical in Toll-like receptor-mediated cell motility in macrophages. Biochim Biophys Acta 1813, 136–147, doi: 10.1016/j.bbamcr.2010.09.004 (2011).
    Martinez, F. O. & Gordon, S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 6, 13, doi: 10.12703/P6-13 (2014).
    Hagemann, T. et al. “Re-educating” tumor-associated macrophages by targeting NF-kappaB. J Exp Med 205, 1261–1268, doi: 10.1084/jem.20080108 (2008).
    Kleveta, G. et al. LPS induces phosphorylation of actin-regulatory proteins leading to actin reassembly and macrophage motility. J Cell Biochem 113, 80–92, doi: 10.1002/jcb.23330 (2012).
    Devitt, A. et al. Human CD14 mediates recognition and phagocytosis of apoptotic cells. Nature 392, 505–509, doi: 10.1038/33169 (1998).
    Hawley, K. L. et al. CD14 cooperates with complement receptor 3 to mediate MyD88-independent phagocytosis of Borrelia burgdorferi. Proc Natl Acad Sci USA 109, 1228–1232, doi: 10.1073/pnas.1112078109 (2012).
    Pereira-da-Silva, G. et al. Neutrophil activation induced by the lectin KM+ involves binding to CXCR2. Biochim Biophys Acta 1760, 86–94, doi: 10.1016/j.bbagen.2005.09.011 (2006).
    Ricci-Azevedo, R., Oliveira, A. F., Conrado, M. C., Carvalho, F. C. & Roque-Barreira, M. C. Neutrophils Contribute to the Protection Conferred by ArtinM against Intracellular Pathogens: A Study on Leishmania major. PLoS Negl Trop Dis 10, e0004609, doi: 10.1371/journal.pntd.0004609 (2016).
    Kawai, T. & Akira, S. Signaling to NF-kappaB by Toll-like receptors. Trends Mol Med 13, 460–469, doi: 10.1016/j.molmed.2007.09.002 (2007).
    Bowie, A. & O’Neill, L. A. Oxidative stress and nuclear factor-kappaB activation: a reassessment of the evidence in the light of recent discoveries. Biochem Pharmacol 59, 13–23 (2000).
    Barbosa-Lorenzi, V. C. et al. The lectin ArtinM binds to mast cells inducing cell activation and mediator release. Biochem Biophys Res Commun 416, 318–324, doi: 10.1016/j.bbrc.2011.11.033 (2011).
    Pugin, J. et al. CD14 is a pattern recognition receptor. Immunity 1, 509–516 (1994).
    Yan, S. R., Al-Hertani, W., Byers, D. & Bortolussi, R. Lipopolysaccharide-binding protein- and CD14-dependent activation of mitogen-activated protein kinase p38 by lipopolysaccharide in human neutrophils is associated with priming of respiratory burst. Infect Immun 70, 4068–4074 (2002).
    Kesherwani, V. & Sodhi, A. Differential activation of macrophages in vitro by lectin Concanavalin A, Phytohemagglutinin and Wheat germ agglutinin: production and regulation of nitric oxide. Nitric Oxide 16, 294–305, doi: 10.1016/j.niox.2006.11.001 (2007).
    Flo, T. H. et al. Differential expression of Toll-like receptor 2 in human cells. J Leukoc Biol 69, 474–481 (2001).
    Shin, H. S., Lee, J. H., Paek, S. H., Jung, Y. W. & Ha, U. H. Pseudomonas aeruginosa-dependent upregulation of TLR2 influences host responses to a secondary Staphylococcus aureus infection. Pathog Dis 69, 149–156, doi: 10.1111/2049-632X.12074 (2013).
    Mifsud, E. J., Tan, A. C. & Jackson, D. C. TLR Agonists as Modulators of the Innate Immune Response and Their Potential as Agents Against Infectious Disease. Front Immunol 5, 79, doi: 10.3389/fimmu.2014.00079 (2014).
    Green, L. C. et al. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126, 131–138 (1982).
    Adam, E. et al. The house dust mite allergen Der p 1, unlike Der p 3, stimulates the expression of interleukin-8 in human airway epithelial cells via a proteinase-activated receptor-2-independent mechanism. J Biol Chem 281, 6910–6923, doi: 10.1074/jbc.M507140200 (2006).
    Carneiro, A. B. et al. Lysophosphatidylcholine triggers TLR2- and TLR4-mediated signaling pathways but counteracts LPS-induced NO synthesis in peritoneal macrophages by inhibiting NF-kappaB translocation and MAPK/ERK phosphorylation. PLoS One 8, e76233, doi: 10.1371/journal.pone.0076233 (2013).
    Juliano, R. L. & Li, G. Glycoproteins of the CHO cell membrane: partial fractionation of the receptors for concanavalin A and wheat germ agglutinin using a lectin immunoprecipitation technique. Biochemistry 17, 678–683 (1978).