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Activation of natural killer cells during acute infection with hepatitis C virus

Activation of natural killer cells during acute infection with hepatitis C virus
Activation of natural killer cells during acute infection with hepatitis C virus
Background & Aims
Natural killer (NK) cells are essential early after infection, not only for viral containment but also for timely and efficient induction of adaptive responses. An inhibitory effect of hepatitis C virus (HCV)-E2 proteins on NK cells has been reported, but the features of NK cell responses in the acute phase of hepatitis C are still largely undefined. Therefore, the aim of this study was to characterize the function and phenotype of NK cells in the acute phase of infection and compare individuals with chronic and self-limited outcomes.

Methods
Twenty-two individuals with acute HCV infection, 14 with chronic evolution, and 8 with self-limited infection, were studied using NK phenotypic and functional assays.

Results
An increased expression of NKG2D on both CD56bright and CD56dim NK cells was detected in patients with acute HCV, irrespective of the outcome, as compared with healthy controls. Also, interferon gamma production and cytotoxicity by NK cells were higher in individuals with acute HCV infection than in healthy controls. Subset analysis showed increased interferon gamma production in both NK cell subsets carrying group 1 and group 2 HLA-C–specific killer cell immunoglobulin-like receptors. However, increased CD107a was noted only on NK cells expressing the group 1 HLA-C–specific killer cell immunoglobulin-like receptor and was maximal in self-limited infection.

Conclusions
Our data show that in the acute phase of HCV infection, NK cells are activated regardless of outcome, with no evidence of a suppressive effect of HCV on NK cell function.

NK receptors, cytotoxicity, interferon gamma
0016-5085
1536-1545
Amadei, Barbara
3170c767-c1bb-4d69-934f-c365cd577fdb
Urbani, Simona
e2918e20-fafe-468a-8674-a0d8ccf9d7d1
Cazaly, Angelica
944b91cc-ab19-463c-ad08-a6b04c6e628d
Fisicaro, Paola
529c9177-8ad2-4e4c-855d-80a16fe19e05
Zerbini, Alessandro
b4f34dfb-5a8f-4c98-8a87-da9dfd3c3675
Ahmed, Parvin
77517b39-60b4-4c28-987c-75d70cc362ff
Missale, Gabriele
b1169348-5f5e-497b-ac6c-98d5bfe41ac3
Ferrari, Carlo
87e93597-5f73-4905-9c22-65496d1e9a42
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Amadei, Barbara
3170c767-c1bb-4d69-934f-c365cd577fdb
Urbani, Simona
e2918e20-fafe-468a-8674-a0d8ccf9d7d1
Cazaly, Angelica
944b91cc-ab19-463c-ad08-a6b04c6e628d
Fisicaro, Paola
529c9177-8ad2-4e4c-855d-80a16fe19e05
Zerbini, Alessandro
b4f34dfb-5a8f-4c98-8a87-da9dfd3c3675
Ahmed, Parvin
77517b39-60b4-4c28-987c-75d70cc362ff
Missale, Gabriele
b1169348-5f5e-497b-ac6c-98d5bfe41ac3
Ferrari, Carlo
87e93597-5f73-4905-9c22-65496d1e9a42
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273

Amadei, Barbara, Urbani, Simona, Cazaly, Angelica, Fisicaro, Paola, Zerbini, Alessandro, Ahmed, Parvin, Missale, Gabriele, Ferrari, Carlo and Khakoo, Salim I. (2010) Activation of natural killer cells during acute infection with hepatitis C virus. Gastroenterology, 138 (4), 1536-1545. (doi:10.1053/j.gastro.2010.01.006). (PMID:20080094)

Record type: Article

Abstract

Background & Aims
Natural killer (NK) cells are essential early after infection, not only for viral containment but also for timely and efficient induction of adaptive responses. An inhibitory effect of hepatitis C virus (HCV)-E2 proteins on NK cells has been reported, but the features of NK cell responses in the acute phase of hepatitis C are still largely undefined. Therefore, the aim of this study was to characterize the function and phenotype of NK cells in the acute phase of infection and compare individuals with chronic and self-limited outcomes.

Methods
Twenty-two individuals with acute HCV infection, 14 with chronic evolution, and 8 with self-limited infection, were studied using NK phenotypic and functional assays.

Results
An increased expression of NKG2D on both CD56bright and CD56dim NK cells was detected in patients with acute HCV, irrespective of the outcome, as compared with healthy controls. Also, interferon gamma production and cytotoxicity by NK cells were higher in individuals with acute HCV infection than in healthy controls. Subset analysis showed increased interferon gamma production in both NK cell subsets carrying group 1 and group 2 HLA-C–specific killer cell immunoglobulin-like receptors. However, increased CD107a was noted only on NK cells expressing the group 1 HLA-C–specific killer cell immunoglobulin-like receptor and was maximal in self-limited infection.

Conclusions
Our data show that in the acute phase of HCV infection, NK cells are activated regardless of outcome, with no evidence of a suppressive effect of HCV on NK cell function.

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More information

e-pub ahead of print date: 18 January 2010
Published date: April 2010
Keywords: NK receptors, cytotoxicity, interferon gamma
Organisations: Cancer Sciences, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 336180
URI: http://eprints.soton.ac.uk/id/eprint/336180
ISSN: 0016-5085
PURE UUID: b5fb224e-8fa2-4e88-9d3a-11e5bd657681
ORCID for Salim I. Khakoo: ORCID iD orcid.org/0000-0002-4057-9091

Catalogue record

Date deposited: 16 Mar 2012 12:41
Last modified: 15 Mar 2024 03:12

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Contributors

Author: Barbara Amadei
Author: Simona Urbani
Author: Angelica Cazaly
Author: Paola Fisicaro
Author: Alessandro Zerbini
Author: Parvin Ahmed
Author: Gabriele Missale
Author: Carlo Ferrari
Author: Salim I. Khakoo ORCID iD

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