Patrizia Leone1, Mariangela Di Tacchio1, Simona Berardi1, Teresa Santantonio2, Massimo Fasano2, Soldano Ferrone3, Angelo Vacca1, Franco Dammacco1, Vito Racanelli4. 1. Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy. 2. Department of Infectious Diseases, University of Foggia, Foggia, Italy. 3. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 4. Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy. Electronic address: vito.racanelli1@uniba.it.
Abstract
BACKGROUND & AIMS: Modulation of dendritic cell (DC) function has been theorized as one of the mechanisms used by hepatitis C virus (HCV) to evade the host immune response and cause persistent infection. METHODS: We used a range of cell and molecular biology techniques to study DC subsets from uninfected and HCV-infected individuals. RESULTS: We found that patients with persistent HCV infection have lower numbers of circulating myeloid DC and plasmacytoid DC than healthy controls or patients who spontaneously recovered from HCV infection. Nonetheless, DC from patients with persistent HCV infection display normal phagocytic activity, typical expression of the class I and II HLA and co-stimulatory molecules, and conventional cytokine production when stimulated to mature in vitro. In contrast, they do not display the strong switch from immunoproteasome to standard proteasome subunit expression and the upregulation of the transporter-associated proteins following stimulation, which were instead observed in DC from uninfected individuals. This different modulation of components of the HLA class I antigen processing-presenting machinery results in a differential ability to present a CD8(+) T cell epitope whose generation is dependent on the LMP7 immunoproteasome subunit. CONCLUSIONS: Overall, these findings establish that under conditions of persistent HCV antigenemia, HLA class I antigen processing and presentation are distinctively regulated during DC maturation.
BACKGROUND & AIMS: Modulation of dendritic cell (DC) function has been theorized as one of the mechanisms used by hepatitis C virus (HCV) to evade the host immune response and cause persistent infection. METHODS: We used a range of cell and molecular biology techniques to study DC subsets from uninfected and HCV-infected individuals. RESULTS: We found that patients with persistent HCV infection have lower numbers of circulating myeloid DC and plasmacytoid DC than healthy controls or patients who spontaneously recovered from HCV infection. Nonetheless, DC from patients with persistent HCV infection display normal phagocytic activity, typical expression of the class I and II HLA and co-stimulatory molecules, and conventional cytokine production when stimulated to mature in vitro. In contrast, they do not display the strong switch from immunoproteasome to standard proteasome subunit expression and the upregulation of the transporter-associated proteins following stimulation, which were instead observed in DC from uninfected individuals. This different modulation of components of the HLA class I antigen processing-presenting machinery results in a differential ability to present a CD8(+) T cell epitope whose generation is dependent on the LMP7 immunoproteasome subunit. CONCLUSIONS: Overall, these findings establish that under conditions of persistent HCV antigenemia, HLA class I antigen processing and presentation are distinctively regulated during DC maturation.
Authors: Loems Ziegler-Heitbrock; Petronela Ancuta; Suzanne Crowe; Marc Dalod; Veronika Grau; Derek N Hart; Pieter J M Leenen; Yong-Jun Liu; Gordon MacPherson; Gwendalyn J Randolph; Juergen Scherberich; Juergen Schmitz; Ken Shortman; Silvano Sozzani; Herbert Strobl; Marek Zembala; Jonathan M Austyn; Manfred B Lutz Journal: Blood Date: 2010-07-13 Impact factor: 22.113
Authors: Ioannis Pachiadakis; Shilpa Chokshi; Helen Cooksley; Dimitrios Farmakiotis; Christoph Sarrazin; Stefan Zeuzem; Tomasz I Michalak; Nikolai V Naoumov Journal: Clin Immunol Date: 2009-03-20 Impact factor: 3.969
Authors: María I Crespo; Estefanía R Zacca; Nicolás G Núñez; Romina P Ranocchia; Mariana Maccioni; Belkys A Maletto; María C Pistoresi-Palencia; Gabriel Morón Journal: J Immunol Date: 2013-01-02 Impact factor: 5.422
Authors: Donald D Anthony; Nicole L Yonkers; Anthony B Post; Robert Asaad; Frederick P Heinzel; Michael M Lederman; Paul V Lehmann; Hernan Valdez Journal: J Immunol Date: 2004-04-15 Impact factor: 5.422
Authors: Fatma Mohamed El-Esawy; Heba Mohamed Abd El-Kareem; Ayman Abdell-All Mohamady; Amany Mohammed Mohammed Agamy; Rehab Mohammed Salem Journal: J Clin Aesthet Dermatol Date: 2021-12