Research

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Ivan Zanoni, MD

Ivan Zanoni
Lab:
Zanoni Laboratory
Department:
Medicine Research
Division
Gastroenterology, Hepatology and Nutrition Research
Hospital Title:
Staff Scientist
Academic Title:
Assistant Professor, Harvard Medical School
Research Focus Area:
Inflammatory disordersInnate immunity
Contact Via Email
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Research 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.

About Ivan Zanoni:

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).

Publications

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  1. 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; (110):e52589.
  2. 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.
  3. Brubaker SW, Bonham KS, Zanoni I, Kagan JC. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol. 2015; 33:257-90.
  4. 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.
  5. 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.
  6. 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.
  7. Granucci F, Lutz MB, Zanoni I. The nature of activatory and tolerogenic dendritic cell-derived signal 2. Front Immunol. 2014; 5:42.
  8. 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.
  9. 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.
  10. 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.
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  12. 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.
  13. 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.
  14. Zanoni I, Granucci F. Role of CD14 in host protection against infections and in metabolism regulation. Front Cell Infect Microbiol. 2013; 3:32.
  15. Granucci F, Lutz MB, Zanoni I. The nature of activatory and tolerogenic dendritic cell-derived signal 2. Front Immunol. 2013; 4:198.
  16. 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.
  17. 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 3; 51(23):12776-88.
  18. 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.
  19. 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.
  20. 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 9; 120(6):1237-45.
  21. 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.
  22. 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.
  23. 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.
  24. 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; 5(8):e12216.
  25. Ostuni R, Zanoni I, Granucci F. Deciphering the complexity of Toll-like receptor signaling. Cell Mol Life Sci. 2010 Dec; 67(24):4109-34.
  26. 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.
  27. 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.
  28. 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.
  29. Zanoni I, Granucci F. Differences in lipopolysaccharide-induced signaling between conventional dendritic cells and macrophages. Immunobiology. 2010 Sep-Oct; 215(9-10):709-12.
  30. Granucci F, Zanoni I. The dendritic cell life cycle. Cell Cycle. 2009 Dec; 8(23):3816-21.
  31. 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 9; 460(7252):264-8.
  32. 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.
  33. Granucci F, Zanoni I. Role of Toll like receptor-activated dendritic cells in the development of autoimmunity. Front Biosci. 2008; 13:4817-26.
  34. 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.
  35. 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.
  36. 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.
  37. 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.
  38. 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 1; 176(7):4012-20.
  39. 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 1; 176(7):4021-8.
  40. 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 1; 175(1):286-92.
  41. 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 2; 200(3):287-95.
  42. 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.
  43. 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.
  44. 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 2; 22(11):2546-51.
  45. 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.
  46. 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.
  47. 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.
  48. 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.
  49. 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.
  50. 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.
  51. 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.
  52. 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 9; 18(6):682-93.
  53. 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 3; 352(6290):1232-6.
  54. 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 Sep 01; 8(9):1039-51.
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