Immunology, Transplantation and Infectious diseases

Immunopathology

Group leader

Luca Guidotti

Research programs of Immunopathology Unit aim to dissect the cellular and molecular mechanisms responsible for immunopathological responses of the liver, with emphasis on the responses that occur during infection with hepatitis B virus (HBV). HBV is a noncytopathic virus that cause acute and chronic hepatitis of variable duration and severity. Over 250 million people worldwide are chronically infected by HBV and almost a million of them die each year from complications (e.g. cirrhosis and hepatocellular carcinoma, HCC) of this infection.

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Research activity

Taking advantage of infected patients, proprietary animal models of infection and new technological advances in the field of static and dynamic imaging, Immunopathology Unit tackles unresolved issues that include the means by which innate and adaptive immune cells traffic and function within the normal, cirrhotic or cancerous livers. This information is and will be used to devise novel immunotherapeutic strategies to cure chronic HBV infection and prevent its life-threatening sequelae.

Selected publications

Guidotti LG, Inverso D, Sironi L, Di Lucia P, Fioravanti J, Ganzer L, Fiocchi A, Vacca M, Aiolfi R, Sammicheli S, Mainetti M, Cataudella T, Raimondi A, Gonzalez- Aseguinolaza G, Protzer U, Chisari FV, Ruggeri ZM, Isogawa M, Sitia G, Iannacone M. Immunosurveillance of the liver by intravascular effector CD8+ T cells. Cell 2015 Apr 23;161(3):486-500. IF: 33.116.

Sitia G, Aiolfi R, Di Lucia P, Mainetti M, Fiocchi A, Mingozzi F, Esposito A, Ruggeri ZM, Chisari FV, Iannacone M and Guidotti LG. Anti-platelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B. PNAS Plus, USA. 2012 Aug 7;109(32):E2165-72. IF: 9.809.

Sitia G, Iannacone M, Aiolfi R, Isogawa M, van Rooijen N, Scozzesi C, Bianchi ME, von Andrian UH, Chisari FV, Guidotti LG. Kupffer cells hasten resolution of liver immunopathology in mouse models of viral hepatitis. Plos Pathogens. 2011; 7(6):e1002061.

Iannacone M, Moseman EA, Tonti E, Bosurgi L, Junt T, Henrickson SE, Whelan SP, Guidotti LG, von Andrian UH. Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus. Nature. 2010 Jun; 465(7301):1079-83.

Iannacone M, Sitia G, Isogawa M, Whitmire JK, Marchese P, Chisari FV, Ruggeri ZM, Guidotti LG. Platelets prevent IFN-a/b-induced lethal hemorrhage promoting CTL- dependent clearance of lymphocytic choriomeningitis virus. Proc. Natl Acad. Sci USA. 2008; 105 (2) 629-634.

Guidotti LG, Chisari FV. Immunobiology and pathogenesis of viral hepatitis. Review. Annu Rev. Pathology. 2006; 1:23-61.

Iannacone M, Sitia G, Isogawa M, Marchese P, Castro MG, Lowenstein PR, Chisari FV, Ruggeri ZM, Guidotti LG. Platelets mediate cytotoxic T lymphocyte-induced liver damage. Nat Med. 2005 Nov;11(11):1167-9.

Sitia G, Isogawa M, Iannacone M, Campbell IL, Chisari FV, Guidotti LG. MMPs are required for recruitment of antigen non-specific mononuclear cells into the liver by CTLs. J Clinical Investigation. 2004 Apr 15; 113(8): 1158–1167.

Sitia G, Isogawa M, Kakimi K, Wieland SF, Chisari FV, Guidotti LG. Depletion of neutrophils blocks the recruitment of antigen non-specific cells into the liver without affecting the antiviral activity of hepatitis B virus-specific cytotoxic T lymphocytes. Proc Nat Acad Sci USA. 2002 Oct 15;99(21):13717-22.

Kakimi K, Lane TE, Wieland SF, Asensio VC, Campbell IL, Chisari FV, Guidotti LG. Blocking chemokine responsive to {gamma}–2/interferon (IFN)-{gamma} inducible protein and monokine induced by IFN-{gamma} activity in vivo reduces the pathogenetic but not the antiviral potential of hepatitis B virus–specific cytotoxic T lymphocytes. J Exp Med. 2001 Dec 17;194(12):1755-66.

Guidotti LG, Chisari FV. Noncytolytic control of viral infections by the innate and adaptive immune response. Review. Annu Rev Immunol. 2001.19:65-91.