Early kinetics of innate and adaptive immune responses during hepatitis B virus infection

P. Fisicaro, C. Valdatta, C. Boni, M. Massari, C. Mori, A. Zerbini, A. Orlandini, L. Sacchelli, G. Missale, C. Ferrari

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

Background and Aim: Innate immunity appears to be silent in acutely heptitis B virus (HBV)-infected chimpanzees, as shown by microarray analysis of intrahepatic gene expression. Whether this observation also applies to HBV pathogenesis in man remains undefined. The aim of this study was thus to characterise natural killer (NK) and CD56+ natural T (NT) cell responses early after human HBV infection and their relationship to the induction of adaptive immunity. Methods: Two HBV-seronegative blood donors who became hepatitis B surface antigen (HBsAg) and HBV DNA positive but had persistently normal alanine aminotransferase (ALT) were followed from a very early stage of HBV infection. The phenotype (CD69 and NKG2D) and function (cytotoxicity and interferon γ (IFNγ) production) of NK and NT cells were analysed. CD4- and CD8-mediated responses were studied in parallel with overlapping peptides covering the entire HBV sequence by ex vivo intracellular cytokine staining (ICS) for IFNγ, interleukin 2 (IL2), IL4 and IL10, and by ex vivo Elispot for IFNc. Healthy subjects, and patients with chronic and acute HBV infection were studied for comparison. Results: An early induction of both innate and adaptive responses was observed. NK and NT cells showed faster kinetics than HBV-specific T cells with an earlier peak of activity, while CD4+ and CD8+ cell responses were mounted with a similar profile, with higher frequencies of IFNγ-producing CD8+ cells at the peak of the response. Conclusions: The innate immune system is able to sense HBV infection, as shown by the early development of NK and NT cell responses, which probably contribute to contain the HBV infection and to allow timely induction of adaptive responses.

Original languageEnglish
Pages (from-to)974-982
Number of pages9
JournalGut
Volume58
Issue number7
DOIs
Publication statusPublished - Jul 2009

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Cercopithecine Herpesvirus 1
Adaptive Immunity
Virus Diseases
Innate Immunity
Hepatitis B virus
Natural Killer T-Cells
Interferons
Pan troglodytes
Microarray Analysis
Hepatitis B Surface Antigens
Blood Donors
Alanine Transaminase
Interleukin-4
Interleukin-10
Interleukin-2
Immune System
Healthy Volunteers

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Fisicaro, P., Valdatta, C., Boni, C., Massari, M., Mori, C., Zerbini, A., ... Ferrari, C. (2009). Early kinetics of innate and adaptive immune responses during hepatitis B virus infection. Gut, 58(7), 974-982. https://doi.org/10.1136/gut.2008.163600

Early kinetics of innate and adaptive immune responses during hepatitis B virus infection. / Fisicaro, P.; Valdatta, C.; Boni, C.; Massari, M.; Mori, C.; Zerbini, A.; Orlandini, A.; Sacchelli, L.; Missale, G.; Ferrari, C.

In: Gut, Vol. 58, No. 7, 07.2009, p. 974-982.

Research output: Contribution to journalArticle

Fisicaro, P, Valdatta, C, Boni, C, Massari, M, Mori, C, Zerbini, A, Orlandini, A, Sacchelli, L, Missale, G & Ferrari, C 2009, 'Early kinetics of innate and adaptive immune responses during hepatitis B virus infection', Gut, vol. 58, no. 7, pp. 974-982. https://doi.org/10.1136/gut.2008.163600
Fisicaro P, Valdatta C, Boni C, Massari M, Mori C, Zerbini A et al. Early kinetics of innate and adaptive immune responses during hepatitis B virus infection. Gut. 2009 Jul;58(7):974-982. https://doi.org/10.1136/gut.2008.163600
Fisicaro, P. ; Valdatta, C. ; Boni, C. ; Massari, M. ; Mori, C. ; Zerbini, A. ; Orlandini, A. ; Sacchelli, L. ; Missale, G. ; Ferrari, C. / Early kinetics of innate and adaptive immune responses during hepatitis B virus infection. In: Gut. 2009 ; Vol. 58, No. 7. pp. 974-982.
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