ABOUT THE RESEARCHER

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).

PUBLICATIONS

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  1. The interferon landscape along the respiratory tract impacts the severity of COVID-19. Cell. 2021 09 16; 184(19):4953-4968.e16. View abstract
  2. Interfering with SARS-CoV-2: are interferons friends or foes in COVID-19? Curr Opin Virol. 2021 10; 50:119-127. View abstract
  3. Aged vasculature drives neutrophils mad. Immunity. 2021 07 13; 54(7):1369-1371. View abstract
  4. Dissecting the common and compartment-specific features of COVID-19 severity in the lung and periphery with single-cell resolution. iScience. 2021 Jul 23; 24(7):102738. View abstract
  5. Alum:CpG adjuvant enables SARS-CoV-2 RBD-induced protection in aged mice and synergistic activation of human elder type 1 immunity. bioRxiv. 2021 May 21. View abstract
  6. Notch4 signaling limits regulatory T-cell-mediated tissue repair and promotes severe lung inflammation in viral infections. Immunity. 2021 06 08; 54(6):1186-1199.e7. View abstract
  7. Viral Respiratory Pathogens and Lung Injury. Clin Microbiol Rev. 2021 06 16; 34(3). View abstract
  8. Inositol 1,4,5-trisphosphate 3-kinase B promotes Ca2+ mobilization and the inflammatory activity of dendritic cells. Sci Signal. 2021 Mar 30; 14(676). View abstract
  9. Severity of SARS-CoV-2 infection as a function of the interferon landscape across the respiratory tract of COVID-19 patients. bioRxiv. 2021 Mar 30. View abstract
  10. Dooming Phagocyte Responses: Inflammatory Effects of Endogenous Oxidized Phospholipids. Front Endocrinol (Lausanne). 2021; 12:626842. View abstract
  11. Deep-sea microbes as tools to refine the rules of innate immune pattern recognition. Sci Immunol. 2021 Mar 12; 6(57). View abstract
  12. JEM career launchpad. J Exp Med. 2021 02 01; 218(2). View abstract
  13. Efficient treatment of a preclinical inflammatory bowel disease model with engineered bacteria. Mol Ther Methods Clin Dev. 2021 Mar 12; 20:218-226. View abstract
  14. Inflammasomes within Hyperactive Murine Dendritic Cells Stimulate Long-Lived T Cell-Mediated Anti-tumor Immunity. Cell Rep. 2020 11 17; 33(7):108381. View abstract
  15. Targeting innate immunity by blocking CD14: Novel approach to control inflammation and organ dysfunction in COVID-19 illness. EBioMedicine. 2020 Jul; 57:102836. View abstract
  16. Type III interferons disrupt the lung epithelial barrier upon viral recognition. Science. 2020 08 07; 369(6504):706-712. View abstract
  17. COVID-19 and emerging viral infections: The case for interferon lambda. J Exp Med. 2020 05 04; 217(5). View abstract
  18. Cellular and molecular mechanisms of antifungal innate immunity at epithelial barriers: The role of C-type lectin receptors. Eur J Immunol. 2020 03; 50(3):317-325. View abstract
  19. Microbiome studies in the medical sciences and the need for closer multidisciplinary interplay. Sci Signal. 2020 02 04; 13(617). View abstract
  20. Type III interferons: Balancing tissue tolerance and resistance to pathogen invasion. J Exp Med. 2020 01 06; 217(1). View abstract
  21. Endogenous oxidized phospholipids reprogram cellular metabolism and boost hyperinflammation. Nat Immunol. 2020 01; 21(1):42-53. View abstract
  22. 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
  23. Editorial: Interferon-?s: New Regulators of Inflammatory Processes. Front Immunol. 2019; 10:2117. View abstract
  24. Are nanotechnological approaches the future of treating inflammatory diseases? Nanomedicine (Lond). 2019 09; 14(17):2379-2390. View abstract
  25. Below the surface: The inner lives of TLR4 and TLR9. J Leukoc Biol. 2019 07; 106(1):147-160. View abstract
  26. Lambda interferons come to light: dual function cytokines mediating antiviral immunity and damage control. Curr Opin Immunol. 2019 02; 56:67-75. View abstract
  27. Intersection of phosphate transport, oxidative stress and TOR signalling in Candida albicans virulence. PLoS Pathog. 2018 07; 14(7):e1007076. View abstract
  28. Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines. Front Immunol. 2018; 9:1484. View abstract
  29. Deep Dermal Injection As a Model of Candida albicans Skin Infection for Histological Analyses. J Vis Exp. 2018 06 13; (136). View abstract
  30. 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
  31. 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
  32. Interferon (IFN)-? Takes the Helm: Immunomodulatory Roles of Type III IFNs. Front Immunol. 2017; 8:1661. View abstract
  33. 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
  34. Skin infections are eliminated by cooperation of the fibrinolytic and innate immune systems. Sci Immunol. 2017 Sep 22; 2(15). View abstract
  35. Drug nanocarriers to treat autoimmunity and chronic inflammatory diseases. Semin Immunol. 2017 12; 34:61-67. View abstract
  36. IFN-? suppresses intestinal inflammation by non-translational regulation of neutrophil function. Nat Immunol. 2017 Oct; 18(10):1084-1093. View abstract
  37. 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
  38. 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
  39. An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. Science. 2016 Jun 03; 352(6290):1232-6. View abstract
  40. Preparation of Single-cell Suspensions for Cytofluorimetric Analysis from Different Mouse Skin Regions. J Vis Exp. 2016 Apr 20; (110):e52589. View abstract
  41. A Single Bacterial Immune Evasion Strategy Dismantles Both MyD88 and TRIF Signaling Pathways Downstream of TLR4. . 2015 Dec 09; 18(6):682-93. View abstract
  42. 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
  43. Cream formulation impact on topical administration of engineered colloidal nanoparticles. PLoS One. 2015; 10(5):e0126366. View abstract
  44. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol. 2015; 33:257-90. View abstract
  45. Toll-like receptor co-receptors as master regulators of the immune response. Mol Immunol. 2015 Feb; 63(2):143-52. View abstract
  46. 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
  47. rBet v 1 immunotherapy of sensitized mice with Streptococcus thermophilus as vehicle and adjuvant. Hum Vaccin Immunother. 2014; 10(5):1228-37. View abstract
  48. The nature of activatory and tolerogenic dendritic cell-derived signal 2. Front Immunol. 2014; 5:42. View abstract
  49. 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
  50. Modulation of CD14 and TLR4·MD-2 activities by a synthetic lipid A mimetic. Chembiochem. 2014 Jan 24; 15(2):250-8. View abstract
  51. Modeling leukocyte-leukocyte non-contact interactions in a lymph node. PLoS One. 2013; 8(10):e76756. View abstract
  52. 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
  53. 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
  54. Migratory conventional dendritic cells in the induction of peripheral T cell tolerance. J Leukoc Biol. 2013 Nov; 94(5):903-11. View abstract
  55. Role of CD14 in host protection against infections and in metabolism regulation. Front Cell Infect Microbiol. 2013; 3:32. View abstract
  56. The nature of activatory and tolerogenic dendritic cell-derived signal 2. Front Immunol. 2013; 4:198. View abstract
  57. 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
  58. 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
  59. 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
  60. 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
  61. 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
  62. CD14 and NFAT mediate lipopolysaccharide-induced skin edema formation in mice. J Clin Invest. 2012 May; 122(5):1747-57. View abstract
  63. 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
  64. CD14 controls the LPS-induced endocytosis of Toll-like receptor 4. Cell. 2011 Nov 11; 147(4):868-80. View abstract
  65. 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
  66. DC-ATLAS: a systems biology resource to dissect receptor specific signal transduction in dendritic cells. Immunome Res. 2010 Nov 19; 6:10. View abstract
  67. 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
  68. 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
  69. Accumulative difference image protocol for particle tracking in fluorescence microscopy tested in mouse lymphonodes. PLoS One. 2010 Aug 17; 5(8):e12216. View abstract
  70. Deciphering the complexity of Toll-like receptor signaling. Cell Mol Life Sci. 2010 Dec; 67(24):4109-34. View abstract
  71. The regulatory role of dendritic cells in the induction and maintenance of T-cell tolerance. Autoimmunity. 2011 Feb; 44(1):23-32. View abstract
  72. 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
  73. 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
  74. Differences in lipopolysaccharide-induced signaling between conventional dendritic cells and macrophages. Immunobiology. 2010 Sep-Oct; 215(9-10):709-12. View abstract
  75. The dendritic cell life cycle. . 2009 Dec; 8(23):3816-21. View abstract
  76. CD14 regulates the dendritic cell life cycle after LPS exposure through NFAT activation. Nature. 2009 Jul 09; 460(7252):264-8. View abstract
  77. 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
  78. Role of Toll like receptor-activated dendritic cells in the development of autoimmunity. Front Biosci. 2008 May 01; 13:4817-26. View abstract
  79. Image filtering for two-photon deep imaging of lymphonodes. Eur Biophys J. 2008 Jul; 37(6):979-87. View abstract
  80. 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
  81. 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
  82. 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
  83. 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
  84. 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
  85. 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
  86. 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
  87. 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
  88. The regulatory role of dendritic cells in the immune response. Int Arch Allergy Immunol. 2004 Jul; 134(3):179-85. View abstract
  89. 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
  90. 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