Overview

Ivan Zanoni laboratory studies innate immune cell biology as a means of understanding the earliest events that initiate immunity to infection or drive the development of immune-mediated diseases. He focused primarily on the study of Pattern Recognition Receptor (PRR) signaling pathways. PRRs initiate all immune responses and activate a network of transcription factors that orchestrate the inflammatory response. The organizing principles that govern PRR signaling are largely unknown and their elucidation will likely answer several fundamental questions about the pathophysiological development of the inflammatory process. His work established the first example of a cellular response to bacterial lipopolysaccharide (LPS) that does not depend on Toll-like Receptor (TLR)4, the prototype of the TLRs that are the best characterized family of PRRs. It has long been dogma that signaling via TLR4 is the only means by which mammalian cells respond to LPS. Ivan Zanoni uncovered that CD14 controls the LPS-induced endocytosis of TLR4, a process that is critical for the signaling functions of this receptor in numerous mammalian cell types. He also found that dendritic cells respond to LPS in a TLR4-independent manner that is important for regulating the activation of the Nuclear Factor of Activated T cells (NFAT). This work blurred the line between innate and adaptive immunity, and documented that NFAT operates in cells of both types of immunity. His findings that TLR4-independent LPS response pathway exists and that CD14 has autonomous signaling capacity open new perspectives on the study of LPS-driven inflammatory diseases and, in general, on the potential of co-receptors to modify and integrate the immune responses elicited by their cognate receptor. Goals of Dr. Zanoni’s research include: Understanding the molecular mechanisms that govern the cross-talk between co-receptors and their cognate receptors; Understanding how NFAT activation in innate immune cells regulates the inflammatory process; Understanding how PRRs signaling contributes to the development of inflammatory diseases and metabolic disorders.

Background

Ivan Zanoni trained with Paola Ricciardi-Castagnoli, receiving his Ph.D. in Immunology from the University of Roma-Tor Vergata (Rome, Italy). He then performed postdoctoral training with Francesca Granucci at the University of Milano-Bicocca (Milan, Italy).

Researcher Services

Researcher Areas

  • Inflammatory disorders
  • Innate immunity

Research Departments

Research Divisions

Researcher Labs

PUBLICATIONS

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  1. Prokunina-Olsson L, Alphonse N, Dickenson RE, Durbin JE, Glenn JS, Hartmann R, Kotenko SV, Lazear HM, O'Brien TR, Odendall C, Onabajo OO, Piontkivska H, Santer DM, Reich NC, Wack A, Zanoni I. COVID-19 and emerging viral infections: The case for interferon lambda. J Exp Med. 2020 05 04; 217(5). View abstract
  2. Borriello F, Zanoni I, Granucci F. Cellular and molecular mechanisms of antifungal innate immunity at epithelial barriers: The role of C-type lectin receptors. Eur J Immunol. 2020 Mar; 50(3):317-325. View abstract
  3. Mancini N, Peri F, Rescigno M, Zanoni I. Microbiome studies in the medical sciences and the need for closer multidisciplinary interplay. Sci Signal. 2020 02 04; 13(617). View abstract
  4. Broggi A, Granucci F, Zanoni I. Type III interferons: Balancing tissue tolerance and resistance to pathogen invasion. J Exp Med. 2020 Jan 06; 217(1). View abstract
  5. Di Gioia M, Spreafico R, Springstead JR, Mendelson MM, Joehanes R, Levy D, Zanoni I. Endogenous oxidized phospholipids reprogram cellular metabolism and boost hyperinflammation. Nat Immunol. 2020 01; 21(1):42-53. View abstract
  6. Pontiroli AE, Ceriani V, Tagliabue E, Zakaria AS, Veronelli A, Folli F, Zanoni I. Bariatric surgery, compared to medical treatment, reduces morbidity at all ages but does not reduce mortality in patients aged?<?43 years, especially if diabetes mellitus is present: a post hoc analysis of two retrospective cohort studies. Acta Diabetol. 2020 Mar; 57(3):323-333. View abstract
  7. Zanoni I, Odendall C. Editorial: Interferon-?s: New Regulators of Inflammatory Processes. Front Immunol. 2019; 10:2117. View abstract
  8. Rizzuto MA, Salvioni L, Rotem R, Colombo M, Zanoni I, Granucci F, Prosperi D. Are nanotechnological approaches the future of treating inflammatory diseases? Nanomedicine (Lond). 2019 09; 14(17):2379-2390. View abstract
  9. Marongiu L, Gornati L, Artuso I, Zanoni I, Granucci F. Below the surface: The inner lives of TLR4 and TLR9. J Leukoc Biol. 2019 07; 106(1):147-160. View abstract
  10. Andreakos E, Zanoni I, Galani IE. Lambda interferons come to light: dual function cytokines mediating antiviral immunity and damage control. Curr Opin Immunol. 2019 02; 56:67-75. View abstract
  11. Liu NN, Uppuluri P, Broggi A, Besold A, Ryman K, Kambara H, Solis N, Lorenz V, Qi W, Acosta-Zaldívar M, Emami SN, Bao B, An D, Bonilla FA, Sola-Visner M, Filler SG, Luo HR, Engström Y, Ljungdahl PO, Culotta VC, Zanoni I, Lopez-Ribot JL, Köhler JR. Intersection of phosphate transport, oxidative stress and TOR signalling in Candida albicans virulence. PLoS Pathog. 2018 07; 14(7):e1007076. View abstract
  12. Gornati L, Zanoni I, Granucci F. Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines. Front Immunol. 2018; 9:1484. View abstract
  13. Santus W, Mingozzi F, Vai M, Granucci F, Zanoni I. Deep Dermal Injection As a Model of Candida albicans Skin Infection for Histological Analyses. J Vis Exp. 2018 06 13; (136). View abstract
  14. Radaelli F, D'Alfonso L, Collini M, Mingozzi F, Marongiu L, Granucci F, Zanoni I, Chirico G, Sironi L. Author Correction: µMAPPS: a novel phasor approach to second harmonic analysis for in vitro-in vivo investigation of collagen microstructure. Sci Rep. 2018 Apr 17; 8(1):6314. View abstract
  15. Radaelli F, D'Alfonso L, Collini M, Mingozzi F, Marongiu L, Granucci F, Zanoni I, Chirico G, Sironi L. µMAPPS: a novel phasor approach to second harmonic analysis for in vitro-in vivo investigation of collagen microstructure. Sci Rep. 2017 12 12; 7(1):17468. View abstract
  16. Zanoni I, Granucci F, Broggi A. Interferon (IFN)-? Takes the Helm: Immunomodulatory Roles of Type III IFNs. Front Immunol. 2017; 8:1661. View abstract
  17. Zanoni I, Tan Y, Di Gioia M, Springstead JR, Kagan JC. By Capturing Inflammatory Lipids Released from Dying Cells, the Receptor CD14 Induces Inflammasome-Dependent Phagocyte Hyperactivation. Immunity. 2017 10 17; 47(4):697-709.e3. View abstract
  18. Santus W, Barresi S, Mingozzi F, Broggi A, Orlandi I, Stamerra G, Vai M, Martorana AM, Polissi A, Köhler JR, Liu N, Zanoni I, Granucci F. Skin infections are eliminated by cooperation of the fibrinolytic and innate immune systems. Sci Immunol. 2017 Sep 22; 2(15). View abstract
  19. Prosperi D, Colombo M, Zanoni I, Granucci F. Drug nanocarriers to treat autoimmunity and chronic inflammatory diseases. Semin Immunol. 2017 12; 34:61-67. View abstract
  20. Broggi A, Tan Y, Granucci F, Zanoni I. IFN-? suppresses intestinal inflammation by non-translational regulation of neutrophil function. Nat Immunol. 2017 Oct; 18(10):1084-1093. View abstract
  21. Rusconi M, Gerardi F, Santus W, Lizio A, Sansone VA, Lunetta C, Zanoni I, Granucci F. Inflammatory role of dendritic cells in Amyotrophic Lateral Sclerosis revealed by an analysis of patients' peripheral blood. Sci Rep. 2017 08 10; 7(1):7853. View abstract
  22. Mingozzi F, Spreafico R, Gorletta T, Cigni C, Di Gioia M, Caccia M, Sironi L, Collini M, Soncini M, Rusconi M, von Andrian UH, Chirico G, Zanoni I, Granucci F. Prolonged contact with dendritic cells turns lymph node-resident NK cells into anti-tumor effectors. EMBO Mol Med. 2016 09; 8(9):1039-51. View abstract
  23. Zanoni I, Tan Y, Di Gioia M, Broggi A, Ruan J, Shi J, Donado CA, Shao F, Wu H, Springstead JR, Kagan JC. An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. Science. 2016 Jun 03; 352(6290):1232-6. View abstract
  24. Broggi A, Cigni C, Zanoni I, Granucci F. Preparation of Single-cell Suspensions for Cytofluorimetric Analysis from Different Mouse Skin Regions. J Vis Exp. 2016 Apr 20; (110):e52589. View abstract
  25. Rosadini CV, Zanoni I, Odendall C, Green ER, Paczosa MK, Philip NH, Brodsky IE, Mecsas J, Kagan JC. A Single Bacterial Immune Evasion Strategy Dismantles Both MyD88 and TRIF Signaling Pathways Downstream of TLR4. Cell Host Microbe. 2015 Dec 09; 18(6):682-93. View abstract
  26. Tan Y, Zanoni I, Cullen TW, Goodman AL, Kagan JC. Mechanisms of Toll-like Receptor 4 Endocytosis Reveal a Common Immune-Evasion Strategy Used by Pathogenic and Commensal Bacteria. Immunity. 2015 Nov 17; 43(5):909-22. View abstract
  27. Santini B, Zanoni I, Marzi R, Cigni C, Bedoni M, Gramatica F, Palugan L, Corsi F, Granucci F, Colombo M. Cream formulation impact on topical administration of engineered colloidal nanoparticles. PLoS One. 2015; 10(5):e0126366. View abstract
  28. Brubaker SW, Bonham KS, Zanoni I, Kagan JC. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol. 2015; 33:257-90. View abstract
  29. Di Gioia M, Zanoni I. Toll-like receptor co-receptors as master regulators of the immune response. Mol Immunol. 2015 Feb; 63(2):143-52. View abstract
  30. Guglielmetti S, Zanoni I, Balzaretti S, Miriani M, Taverniti V, De Noni I, Presti I, Stuknyte M, Scarafoni A, Arioli S, Iametti S, Bonomi F, Mora D, Karp M, Granucci F. Murein lytic enzyme TgaA of Bifidobacterium bifidum MIMBb75 modulates dendritic cell maturation through its cysteine- and histidine-dependent amidohydrolase/peptidase (CHAP) amidase domain. Appl Environ Microbiol. 2014 Sep; 80(17):5170-7. View abstract
  31. Petrarca C, Clemente E, Toto V, Iezzi M, Rossi C, Zanotta S, Mistrello G, Zanoni I, Granucci F, Arioli S, Mora D, Guglielmetti S, Paganelli R, Di Gioacchino M. rBet v 1 immunotherapy of sensitized mice with Streptococcus thermophilus as vehicle and adjuvant. Hum Vaccin Immunother. 2014; 10(5):1228-37. View abstract
  32. Granucci F, Lutz MB, Zanoni I. The nature of activatory and tolerogenic dendritic cell-derived signal 2. Front Immunol. 2014; 5:42. View abstract
  33. Catucci M, Zanoni I, Draghici E, Bosticardo M, Castiello MC, Venturini M, Cesana D, Montini E, Ponzoni M, Granucci F, Villa A. Wiskott-Aldrich syndrome protein deficiency in natural killer and dendritic cells affects antitumor immunity. Eur J Immunol. 2014 Apr; 44(4):1039-45. View abstract
  34. Cighetti R, Ciaramelli C, Sestito SE, Zanoni I, Kubik L, Ardá-Freire A, Calabrese V, Granucci F, Jerala R, Martín-Santamaría S, Jiménez-Barbero J, Peri F. Modulation of CD14 and TLR4·MD-2 activities by a synthetic lipid A mimetic. Chembiochem. 2014 Jan 24; 15(2):250-8. View abstract
  35. Gritti N, Caccia M, Sironi L, Collini M, D'Alfonso L, Granucci F, Zanoni I, Chirico G. Modeling leukocyte-leukocyte non-contact interactions in a lymph node. PLoS One. 2013; 8(10):e76756. View abstract
  36. Zanoni I, Spreafico R, Bodio C, Di Gioia M, Cigni C, Broggi A, Gorletta T, Caccia M, Chirico G, Sironi L, Collini M, Colombo MP, Garbi N, Granucci F. IL-15 cis presentation is required for optimal NK cell activation in lipopolysaccharide-mediated inflammatory conditions. Cell Rep. 2013 Sep 26; 4(6):1235-49. View abstract
  37. Bissa M, Pacchioni SM, Zanotto C, De Giuli Morghen C, Illiano E, Granucci F, Zanoni I, Broggi A, Radaelli A. Systemically administered DNA and fowlpox recombinants expressing four vaccinia virus genes although immunogenic do not protect mice against the highly pathogenic IHD-J vaccinia strain. Virus Res. 2013 Dec 26; 178(2):374-82. View abstract
  38. Broggi A, Zanoni I, Granucci F. Migratory conventional dendritic cells in the induction of peripheral T cell tolerance. J Leukoc Biol. 2013 Nov; 94(5):903-11. View abstract
  39. Zanoni I, Granucci F. Role of CD14 in host protection against infections and in metabolism regulation. Front Cell Infect Microbiol. 2013; 3:32. View abstract
  40. Granucci F, Lutz MB, Zanoni I. The nature of activatory and tolerogenic dendritic cell-derived signal 2. Front Immunol. 2013; 4:198. View abstract
  41. Caprini A, Silva D, Zanoni I, Cunha C, Volontè C, Vescovi A, Gelain F. A novel bioactive peptide: assessing its activity over murine neural stem cells and its potential for neural tissue engineering. N Biotechnol. 2013 Jun 25; 30(5):552-62. View abstract
  42. Maggioni D, Fenili F, D'Alfonso L, Donghi D, Panigati M, Zanoni I, Marzi R, Manfredi A, Ferruti P, D'Alfonso G, Ranucci E. Luminescent rhenium and ruthenium complexes of an amphoteric poly(amidoamine) functionalized with 1,10-phenanthroline. Inorg Chem. 2012 Dec 03; 51(23):12776-88. View abstract
  43. Pontiroli F, Dussurget O, Zanoni I, Urbano M, Beretta O, Granucci F, Ricciardi-Castagnoli P, Cossart P, Foti M. The timing of IFNß production affects early innate responses to Listeria monocytogenes and determines the overall outcome of lethal infection. PLoS One. 2012; 7(8):e43455. View abstract
  44. Zanoni I, Granucci F. Regulation and dysregulation of innate immunity by NFAT signaling downstream of pattern recognition receptors (PRRs). Eur J Immunol. 2012 Aug; 42(8):1924-31. View abstract
  45. Vitali C, Mingozzi F, Broggi A, Barresi S, Zolezzi F, Bayry J, Raimondi G, Zanoni I, Granucci F. Migratory, and not lymphoid-resident, dendritic cells maintain peripheral self-tolerance and prevent autoimmunity via induction of iTreg cells. Blood. 2012 Aug 09; 120(6):1237-45. View abstract
  46. Zanoni I, Ostuni R, Barresi S, Di Gioia M, Broggi A, Costa B, Marzi R, Granucci F. CD14 and NFAT mediate lipopolysaccharide-induced skin edema formation in mice. J Clin Invest. 2012 May; 122(5):1747-57. View abstract
  47. Zanoni I, Bodio C, Broggi A, Ostuni R, Caccia M, Collini M, Venkatesh A, Spreafico R, Capuano G, Granucci F. Similarities and differences of innate immune responses elicited by smooth and rough LPS. Immunol Lett. 2012 Feb 29; 142(1-2):41-7. View abstract
  48. Zanoni I, Ostuni R, Marek LR, Barresi S, Barbalat R, Barton GM, Granucci F, Kagan JC. CD14 controls the LPS-induced endocytosis of Toll-like receptor 4. Cell. 2011 Nov 11; 147(4):868-80. View abstract
  49. Sartorius R, Bettua C, D'Apice L, Caivano A, Trovato M, Russo D, Zanoni I, Granucci F, Mascolo D, Barba P, Del Pozzo G, De Berardinis P. Vaccination with filamentous bacteriophages targeting DEC-205 induces DC maturation and potent anti-tumor T-cell responses in the absence of adjuvants. Eur J Immunol. 2011 Sep; 41(9):2573-84. View abstract
  50. Cavalieri D, Rivero D, Beltrame L, Buschow SI, Calura E, Rizzetto L, Gessani S, Gauzzi MC, Reith W, Baur A, Bonaiuti R, Brandizi M, De Filippo C, D'Oro U, Draghici S, Dunand-Sauthier I, Gatti E, Granucci F, Gündel M, Kramer M, Kuka M, Lanyi A, Melief CJ, van Montfoort N, Ostuni R, Pierre P, Popovici R, Rajnavolgyi E, Schierer S, Schuler G, Soumelis V, Splendiani A, Stefanini I, Torcia MG, Zanoni I, Zollinger R, Figdor CG, Austyn JM. DC-ATLAS: a systems biology resource to dissect receptor specific signal transduction in dendritic cells. Immunome Res. 2010 Nov 19; 6:10. View abstract
  51. Piazza M, Colombo M, Zanoni I, Granucci F, Tortora P, Weiss J, Gioannini T, Prosperi D, Peri F. Uniform lipopolysaccharide (LPS)-loaded magnetic nanoparticles for the investigation of LPS-TLR4 signaling. Angew Chem Int Ed Engl. 2011 Jan 17; 50(3):622-6. View abstract
  52. Guglielmetti S, Taverniti V, Minuzzo M, Arioli S, Zanoni I, Stuknyte M, Granucci F, Karp M, Mora D. A dairy bacterium displays in vitro probiotic properties for the pharyngeal mucosa by antagonizing group A streptococci and modulating the immune response. Infect Immun. 2010 Nov; 78(11):4734-43. View abstract
  53. Villa CE, Caccia M, Sironi L, D'Alfonso L, Collini M, Rivolta I, Miserocchi G, Gorletta T, Zanoni I, Granucci F, Chirico G. Accumulative difference image protocol for particle tracking in fluorescence microscopy tested in mouse lymphonodes. PLoS One. 2010 Aug 17; 5(8):e12216. View abstract
  54. Ostuni R, Zanoni I, Granucci F. Deciphering the complexity of Toll-like receptor signaling. Cell Mol Life Sci. 2010 Dec; 67(24):4109-34. View abstract
  55. Zanoni I, Granucci F. The regulatory role of dendritic cells in the induction and maintenance of T-cell tolerance. Autoimmunity. 2011 Feb; 44(1):23-32. View abstract
  56. Ferri E, Donghi D, Panigati M, Prencipe G, D'Alfonso L, Zanoni I, Baldoli C, Maiorana S, D'Alfonso G, Licandro E. Luminescent conjugates between dinuclear rhenium(I) complexes and peptide nucleic acids (PNA) for cell imaging and DNA targeting. Chem Commun (Camb). 2010 Sep 14; 46(34):6255-7. View abstract
  57. Zanoni I, Granucci F. Regulation of antigen uptake, migration, and lifespan of dendritic cell by Toll-like receptors. J Mol Med (Berl). 2010 Sep; 88(9):873-80. View abstract
  58. Zanoni I, Granucci F. Differences in lipopolysaccharide-induced signaling between conventional dendritic cells and macrophages. Immunobiology. 2010 Sep-Oct; 215(9-10):709-12. View abstract
  59. Granucci F, Zanoni I. The dendritic cell life cycle. Cell Cycle. 2009 Dec; 8(23):3816-21. View abstract
  60. Zanoni I, Ostuni R, Capuano G, Collini M, Caccia M, Ronchi AE, Rocchetti M, Mingozzi F, Foti M, Chirico G, Costa B, Zaza A, Ricciardi-Castagnoli P, Granucci F. CD14 regulates the dendritic cell life cycle after LPS exposure through NFAT activation. Nature. 2009 Jul 09; 460(7252):264-8. View abstract
  61. Granucci F, Zanoni I, Ricciardi-Castagnoli P. Central role of dendritic cells in the regulation and deregulation of immune responses. Cell Mol Life Sci. 2008 Jun; 65(11):1683-97. View abstract
  62. Granucci F, Zanoni I. Role of Toll like receptor-activated dendritic cells in the development of autoimmunity. Front Biosci. 2008 May 01; 13:4817-26. View abstract
  63. Caccia M, Sironi L, Collini M, Chirico G, Zanoni I, Granucci F. Image filtering for two-photon deep imaging of lymphonodes. Eur Biophys J. 2008 Jul; 37(6):979-87. View abstract
  64. Zanoni I, Granucci F, Foti M, Ricciardi-Castagnoli P. Self-tolerance, dendritic cell (DC)-mediated activation and tissue distribution of natural killer (NK) cells. Immunol Lett. 2007 May 15; 110(1):6-17. View abstract
  65. Peri F, Granucci F, Costa B, Zanoni I, Marinzi C, Nicotra F. Inhibition of lipid a stimulated activation of human dendritic cells and macrophages by amino and hydroxylamino monosaccharides. Angew Chem Int Ed Engl. 2007; 46(18):3308-12. View abstract
  66. Granucci F, Zanoni I, Ricciardi-Castagnoli P. Natural killer (NK) cell functions can be strongly boosted by activated dendritic cells (DC). Eur J Immunol. 2006 Oct; 36(10):2819-20. View abstract
  67. Vizzardelli C, Pavelka N, Luchini A, Zanoni I, Bendickson L, Pelizzola M, Beretta O, Foti M, Granucci F, Nilsen-Hamilton M, Ricciardi-Castagnoli P. Effects of dexamethazone on LPS-induced activationand migration of mouse dendritic cells revealed by a genome-wide transcriptional analysis. Eur J Immunol. 2006 Jun; 36(6):1504-15. View abstract
  68. Raimondi G, Zanoni I, Citterio S, Ricciardi-Castagnoli P, Granucci F. Induction of peripheral T cell tolerance by antigen-presenting B cells. I. Relevance of antigen presentation persistence. J Immunol. 2006 Apr 01; 176(7):4012-20. View abstract
  69. Raimondi G, Zanoni I, Citterio S, Ricciardi-Castagnoli P, Granucci F. Induction of peripheral T cell tolerance by antigen-presenting B cells. II. Chronic antigen presentation overrules antigen-presenting B cell activation. J Immunol. 2006 Apr 01; 176(7):4021-8. View abstract
  70. Zanoni I, Foti M, Ricciardi-Castagnoli P, Granucci F. TLR-dependent activation stimuli associated with Th1 responses confer NK cell stimulatory capacity to mouse dendritic cells. J Immunol. 2005 Jul 01; 175(1):286-92. View abstract
  71. Granucci F, Zanoni I, Pavelka N, Van Dommelen SL, Andoniou CE, Belardelli F, Degli Esposti MA, Ricciardi-Castagnoli P. A contribution of mouse dendritic cell-derived IL-2 for NK cell activation. J Exp Med. 2004 Aug 02; 200(3):287-95. View abstract
  72. Granucci F, Zanoni I, Feau S, Capuano G, Ricciardi-Castagnoli P. The regulatory role of dendritic cells in the immune response. Int Arch Allergy Immunol. 2004 Jul; 134(3):179-85. View abstract
  73. Granucci F, Feau S, Zanoni I, Pavelka N, Vizzardelli C, Raimondi G, Ricciardi-Castagnoli P. The immune response is initiated by dendritic cells via interaction with microorganisms and interleukin-2 production. J Infect Dis. 2003 Jun 15; 187 Suppl 2:S346-50. View abstract
  74. Granucci F, Zanoni I, Feau S, Ricciardi-Castagnoli P. Dendritic cell regulation of immune responses: a new role for interleukin 2 at the intersection of innate and adaptive immunity. EMBO J. 2003 Jun 02; 22(11):2546-51. View abstract