U.O. name

Molecular Immunology

Scientific Coordinator

Prof A. De Maria, Prof A. Moretta

Description

Innate immunity and chronic infections by intracellular pathogens (A. De Maria, Bozzano F, Marras F)
. Innate immune system, through its ability to quickly limit the spread of infectious pathogens and to prepare the antigen-specific immune system to efficiently clear pathogen, is crucial during the first phase of the immune response. Natural Killer (NK) cells together with iNKT and Dendritic Cells (DCs) represent one of the major components of the innate immune system and are primarily involved in the responses to intracellular pathogens including viruses, mycobacteria and protozoa.

In this context the main interest of our research unit is represented by 


  1. innate immune responses and editing of adaptive responses by NK cells during HIV infection in different subsets of patients including exposed-uninfected, long-term non-progressor, and immunologically-discordant treated patients,
  2. dissection of the interaction of maturing NK cells with invading host pathogens (including HIV-1, HCV, HSV, Mth, BCG),
  3. analysis of NK cell function in non-human primates (macaques, chimpanzees) with either naturally non-progressing infection, naturally non productive infection or vaccine-induced disease attenuation,
  4. the phenothypical and functional characterization of peripheral NK cells of chronic viremic HCV infected patients before and during immunotherapy,
  5. characterization of innate immune factors driving Mth reactivation in vivo and immune correlates of successful control of mycobacterial infections,
  6. functional and phenotypical analysis of microparticles released by NK cells in plasma and in in vitro culture,
  7. immune escape of Herpesviridae (HSV-1, HSV-2, VZV, CMV), Leishmania and HPV to innate checkpoints and exit from latency.

List of publications

  1. Bozzano F, Marras F, Ascierto ML, Cantoni C, Cenderello G, Dentone C, Di Biagio A, Orofino G, Mantia E, Boni S, De Leo P, Picciotto A, Braido F, Antonini F, Wang E, Marincola F, Moretta L, De Maria A. “Emergency exit” of bone-marrow-resident CD34+DNAM-1brightCXCR4+ committed lymphoid precursors during chronic infection and inflammation supports innate and adaptive immune responses. Nature Communications. Nat Commun. 2015 Oct 5;6:8109. doi: 10.1038/ncomms9109.
  2. Ascierto ML, Bozzano F, Bedognetti D, Marras F, Schechterly C, Matsuura K, Picciotto A, Marenco S, Zhao Y, DeGiorgi V, Sommariva M, Moretta L, Wang E, Alter HJ, Marincola FM, De Maria A. Inherent transcriptional signatures of NK cells are associated with response to IFNα + rivabirin therapy in patients with Hepatitis C Virus. J Transl Med. 2015 Mar 1;13(1):77.
  3. Grauwet K, Cantoni C, Parodi M, De Maria A, Devriendt B, Pende D, Moretta L, Vitale M, Favoreel HW (2014). Modulation of CD112 by the alphaherpesvirus gD protein suppresses DNAM-1-dependent NK cell-mediated lysis of infected cells.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 111, p. 16118-16123, ISSN: 0027-8424, doi: 10.1073/pnas.1409485111 - Articolo in rivista 
  4. Marras F, Bozzano F, Ascierto ML, De Maria A. Baseline and dynamic expression of activating NK cell receptors inn the control of chronic viral infections: the paradigm of HIV-1 and HCV. Front Immunol 2014 2;5:305
  5. Bozzano F, Marras F, De Maria A. Immunology of tuberculosis. Mediterr J Hematol Infect Dis 2014; 6(1)
  6. Bisio F, Bozzano F, Marras F, Di Biagio A, Moretta L, De Maria A. Successfully treated HIV-infected patients have differential expression of NK cell receptors (NKp46 and NKp30) according to AIDS status at presentation. Immunol Lett. 2013 Apr;152(1):16-24. doi: 10.1016/j.imlet.2013.03.003. Epub 2013 Mar 26
  7. Marras F, Nicco E, Bozzano F, Di Biagio A, Dentone C, Pontali E, Boni S, Setti M, Orofino G, Mantia E, Bartolacci V, Bisio F, Riva A, Biassoni R, Moretta L, De Maria A. Natural killer cells in HIV controller patients express an activated effector phenotype and do not up-regulate NKp44 on IL-2 stimulation. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11970-5. doi: 10.1073/pnas.1302090110. Epub 2013 Jul 1
  8. Pilotti E, Bianchi MV, De Maria A, Bozzano F, Romanelli MG, Bertazzoni U, Casoli C .HTLV-1/-2 and HIV-1 co-infections: retroviral interference on host immune status. Front Microbiol. 2013 Dec 23;4:372. eCollection 2013. Review.
  9. Dentone C, Di Biagio A, Parodi A, Bozzano F, Fraccaro P, Signori A, Cenderello G, Mantia E, Orofino G, De Maria A, Filaci G, Fenoglio D. Innate immunity cell activation in virologically suppressed HIV-infected maraviroc-treated patients. AIDS. 2014 Feb 4.
  10. Bozzano F, Marras F, Biassoni R, De Maria A. Natural killer in hepatitis C virus infection. Expert Rev Clin Immunol. 2012 Nov;8(8):775-88. doi: 10.1586/eci.12.71
  11. Marras F, Bozzano F, Bentivoglio G, Ugolotti E, Biassoni R, Moretta L, De Maria A. Receptor modulation and functional activation of human CD34+ Lin- derived immature NK cells in vitro by Mycobacterium bovis Bacillus Calmette –Guerin (BCG). Eur J Immunol. 2012 Sep;42(9):2459-70. doi: 10.1002/eji.201242375. Epub 2012 Jul 2
  12. Marras F, Bozzano F, De Maria A. Involvement of activating NK cell receptors and their modulation in pathogen immunity. J Biomed Biotechnol. 2011;2011:152430. Epub 2011 Aug 11.
  13. Bozzano F, Picciotto A, Costa P, Marras F, Fazio V, Hirsch I, Olive D, Moretta L, De Maria A. Activating NK cell receptor expression/function (NKp30,NKp46,DNAM-1) during chronic viraemic HCV infection is associated with the outcome of combined treatment. Eur J Immunol. 2011 Jun 22. doi: 10.1002/eji.201041361
  14. Bedognetti D, Zoppoli G, Massucco C, Zanardi E, Zupo S, Bruzzone A, Sertoli MR, Balleari E, Racchi O, Messina M, Caltabiano G, Icardi G, Durando P, Marincola FM, F. BOCCARDO, Ferrarini M, Ansaldi F, De Maria A. (2011). Impaired response to influenza vaccine associated with persistent memory B cell depletion in non-Hodgkin's lymphoma patients treated with rituximab-containing regimens. JOURNAL OF IMMUNOLOGY, vol. 186, p. 6044-6055, ISSN: 0022-1767, doi: 10.4049/jimmunol.1004095 - Articolo in rivista 
  15. Bozzano F, Nasi M, Bertoncelli L, Nemes E, Prati F, Marras F, Mussini C, Moretta L, Cossarizza A, De Maria A. NK-cell phenotype at interruption underlies widely divergent duration of CD4+-guided antiretroviral treatment interruption. Int Immunol. 2011 Feb;23(2):109-18. Epub 2011 Jan 7.
  16. De Maria A, Bozzano F, Cantoni C, Moretta L. Revisiting human natural killer cell subset function revealed cytolytic CD56(dim)CD16+ NK cells as rapid producers of abundant IFN-gamma on activation. Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):728-32. Epub 2010 Dec 27.
  17. Rutjens E, Mazza S, Biassoni R, Koopman G, Ugolotti E, Fogli M, Dubbes R, Costa P, Mingari MC, Greenwood EJ, Moretta L, De Maria A, Heeney JL (2010). CD8+ NK cells are predominant in chimpanzees, characterized by high NCR expression and cytokine production, and preserved in chronic HIV-1 infection.. EUROPEAN JOURNAL OF IMMUNOLOGY, vol. 40, p. 1440-1450, ISSN: 0014-2980, doi: 10.1002/eji.200940062 - Articolo in rivista 
  18. Costa P, Bozzano F, Fenoglio D, Beltrame A, Cenderello G, Di Biagio A, Ferrea G, Pagano G, De Maria A. Conserved T cell and natural killer cell function in treatment-experienced adultsreceiving tenofovir plus didanosine as nucleoside reverse transcription inhibitor backbone.Clin Exp Immunol. 2009 Oct;158(1):55-63.(I.F. 3,009).
  19. Bozzano F, Costa P, Passalacqua G, Dodi F, Ravera S, Pagano G, Canonica GW, Moretta L, De Maria A. Functionally relevant decreases in activatory receptor expression on NK cells are associated with pulmonary tuberculosis in vivo and persist after succsssful treatment. Int Immunol 2009 Jul;21(7):779-91. Epub 2009 May 21 (I.F. 3,409)
  20. Costa P, Sivori S, Bozzano F, Martini I, Moretta A, Moretta L, De Maria A. “IFN alphamediated increase in cytolytic activity of maturing NK cell upon exposure to HSV-infected myelomonocytes.” Eur J Immunol. 2008 Dec 16. [Epub ahead of print] (I.F. 5,17
  21. DE MARIA A, FOGLI M, COSTA P, MURDACA G, PUPPO F, MAVILIO D, MORETTA A, MORETTA L (2003). The impaired NK cell cytolytic function in viraemic HIV-1 infection is associated with a reduced surface expression of Natural Cytotoxicity Receptors (NKp46, NKp30 and NKp44). EUROPEAN JOURNAL OF IMMUNOLOGY, vol. 33(9), p. 2410-2418, ISSN: 0014-2980 - Articolo in rivista 
  22. A. DE MARIA, A. FERRARIS, M.GUASTELLA, S. PILIA, C. CANTONI, L. POLERO, M. C. MINGARI, D. BASSETTI D, A.S.FAUCI, L. MORETTA (1997). Expression of HLA-class I-specific inhibitory Natural Killer cell receptors in HIV-specific cytolytic T lymphocytes. Impairment of specific cytolytic functions. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 94, p. 10285-10288, ISSN: 0027-8424 - Articolo in rivista
  23. LUSSO P, A. DE MARIA, MALNATI, M., LORI, F, DEROCCO, S.E., BASELER, M. AND GALLO, R.C. (1991). Induction of CD4 and HIV-1 susceptibility in Human CD8+ T-Lymphocytes by HHV-6. NATURE, vol. 349, p. 533-537, ISSN: 0028-0836 - Articolo in rivista
  

Main research lines

  1. Innate immune responses and editing of adaptive responses by NK cells during HIV infection in different subsets of patients (exposed-uninfected, long-term non-progressing, and immunologically-discordant treated patients) with dissection of the interaction of maturing NK cells with invading host pathogens (including HIV-1, HCV, HSV, HPV, Mth, BCG) and immune escape of Herpesviridae (HSV,VZV, CMA) to innate checkpoints and exit from latency;
  2. The phenothypical and functional characterization of peripheral NK cells of chronic viraemic HCV infected patients before and during immunotherapy;
  3. Chracterization of innate immune factors driving Mth reactivation in vivo and immune correlates of successful control of mycobacterial infections;
  4. Functional and phenotypical analysis of microparticles relesead by NK cells in plasma and in in vitro culture.

Research group ERC sector.

  • LS6_1 Innate Immunity and inflammation
  • LS6_6 Immunogenetics
  • LS6_8 Virology

Internal personnel

Surname Name Department Title Scientific area
Moretta Alessandro DIMES Full Professor BIO 17
De Maria Andrea DISSAL Associate Professor MED 17
Castriconi Roberta DIMES Assistant Professor BIO 17
Sivori Simona DIMES Associate Professor BIO 17
Della Chiesa Mariella DIMES Ricercatore BIO 17

Other personnel

Collaborations

  • Prof Ena Wang, Dept of Transfusion Medicine, National Institutes of Health, Bethesda,USA
  • Prof Francesco Marincola Sidra Medical and Research Centre, Doha, Quatar
  • Dott Ascierto Maria Libera, Dept. of Oncology Johns Hopkins University, Baltimore, USA
  • Prof. Antonio Puccetti, Dept. of Experimental Medicine, Università di Genova e Istituto G Gaslini Genova

  • Prof. Cristina Bottino, Dept. of Experimental Medicine, Università di Genova e Istituto G Gaslini Genova
  • Vincenzo Bronte, Ph.D. Istituto Oncologico Veneto, Padova

  • Prof.Eric Vivier (Marseille,France)

  • Prof.Miguel Lopez Botet (Barcelona,Spain)
  • Prof.Daniel Olive (Marseille,France)
  • Prof.Guido Ferlazzo (Messina,Italy)
  • Prof.Silvia Parolini (Brescia,Italy)

  • Prof.Anthony S.Fauci (Bethesda,USA)

  • Prof.Franco Locatelli (Pavia,Italy)
  • Prof Enrico Maggi (Firenze, Italy)
  • Prof Francesco Annunziato (Firenze, Italy)

Fundings

  • Progetto di ricerche sull'AIDS 1989 12 responsabile operativo (p27) - ISS
  • Progetto di ricerche sull'aids 1993 12 responsabile - iss
  • Progetto di ricerche sull'aids 1994 12 responsabile - iss
  • Bando Nazionale AIDS 2006 45G11 24 Responsabile - ISS
  • Progetti di ricerca di Ateneo Università di Genova, 2003 12 Responsabile - MIUR
  • Progetti di ricerca di Ateneo Università di Genova, 2006 12 Responsabile - MIUR
  • Progetti di ricerca di Ateneo Università di Genova, 2008 12 Respèonsabile - MIUR
  • Progetti di ricerca di Ateneo Università di Genova, 2010 24 Responsabile - MIUR
  • Bando Nazionale AIDS 2009 40H69 24 Responsabile Progetti Finalizzati Sanità 2010 "Impact of NK cell funtion and innateimmune on the out come of CD4+ guided treatment interruptionstyrategies in HIV-1 infected patients treated with successful ART" Responsabile - ISS
  • V Programma nazionale ricerca aids "Italian concerted action for the development of a vaccine against HIV/AIDS (icav)" Natural and adaptive immune responces, including cross-clade responses against candidate vaccine antigens in natural and experimental models of protection relevant to vaccine development. II) Evaluation of correlates of protection in selected pediatric cohorts for the implementation of therapeutic and preventive HIV-1 vaccine strategies. – 2005 - 15 Responsabile
  • ISS Sviluppo di vaccini e biotecnologie innovative per la prevenzione e la cura dell'AIDS (ICAV). 2006. Analysis of NK cell function in non-human primates (macaques, chimpanzees) with either naturally non- Responsabile - ISS - Ricerca Finalizzata 2010 – Ministero della Salute