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Published in: Medical Microbiology and Immunology 5/2014

01-10-2014 | Original Investigation

Increased expressions of NKp44, NKp46 on NK/NKT-like cells are associated with impaired cytolytic function in self-limiting hepatitis E infection

Authors: Rumki Das, Anuradha Tripathy

Published in: Medical Microbiology and Immunology | Issue 5/2014

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Abstract

We have characterized the NK/NKT-like cells in patients with self-limiting hepatitis E infection. The distribution of peripheral NK/NKT-like cells, expressions of activation receptors, cytotoxic potential and effector function of NK/NKT-like cells from fresh peripheral blood mononuclear cells of 86 acute patients, 101 recovered and 54 control individuals were assessed. Activated NKT-like (CD16+ CD56+ CD3+) cells were high in the patient groups. On CD56+ CD3 cells, NKp44 and NKp46 expressions were high in the acute patients, whereas NKp30, NKp44, NKp46 and NKG2D were high in the recovered individuals. On CD56+ CD3+ cells, NKp44, NKp46 and NKG2D expressions were high in the recovered but NKp30 was low in both the patient groups. Collectively, the current study elucidates the role of NK/NKT-like cells demonstrating phenotypic alterations of activated NKT-like cells and activation receptors, lack of CD107a expression and functional impairment of peripheral NK/NKT-like cells in self-limiting hepatitis E infection.
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Literature
2.
go back to reference Krumbholz A, Mohn U, Lange J et al (2012) Prevalence of hepatitis E virus specific antibodies in humans with occupational exposure to pigs. Med Microbiol Immunol 201:239–244PubMedCrossRef Krumbholz A, Mohn U, Lange J et al (2012) Prevalence of hepatitis E virus specific antibodies in humans with occupational exposure to pigs. Med Microbiol Immunol 201:239–244PubMedCrossRef
3.
go back to reference Dremsek P, Wenzel JJ, Johne R et al (2012) Seroprevalence study in forestry workers from eastern Germany using novel genotype 3-and rat hepatitis E virus-specific immunoglobulin G ELISAs. Med Microbiol Immunol 201:189–200PubMedCrossRef Dremsek P, Wenzel JJ, Johne R et al (2012) Seroprevalence study in forestry workers from eastern Germany using novel genotype 3-and rat hepatitis E virus-specific immunoglobulin G ELISAs. Med Microbiol Immunol 201:189–200PubMedCrossRef
4.
go back to reference Srivastava R, Aggarwal R, Jameel S et al (2007) Cellular immune responses in acute hepatitis E virus infection to the viral open reading frame 2 protein. Viral Immunol 20:56–65PubMedCrossRefPubMedCentral Srivastava R, Aggarwal R, Jameel S et al (2007) Cellular immune responses in acute hepatitis E virus infection to the viral open reading frame 2 protein. Viral Immunol 20:56–65PubMedCrossRefPubMedCentral
5.
go back to reference Tripathy AS, Das R, Rathod SB, Arankalle VA (2012) Cytokine profiles, CTL response and T cell frequencies in the peripheral blood of acute patients and individuals recovered from Hepatitis E infection. PLoS ONE 7:e31822PubMedCrossRefPubMedCentral Tripathy AS, Das R, Rathod SB, Arankalle VA (2012) Cytokine profiles, CTL response and T cell frequencies in the peripheral blood of acute patients and individuals recovered from Hepatitis E infection. PLoS ONE 7:e31822PubMedCrossRefPubMedCentral
8.
go back to reference Biron CA, Brossay L (2001) NK cells and NKT cells in innate defense against viral infections. Curr Opin Immunol 13:458–464PubMedCrossRef Biron CA, Brossay L (2001) NK cells and NKT cells in innate defense against viral infections. Curr Opin Immunol 13:458–464PubMedCrossRef
9.
go back to reference Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S (2008) Functions of natural killer cells. Nat Immunol 9:503–510PubMedCrossRef Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S (2008) Functions of natural killer cells. Nat Immunol 9:503–510PubMedCrossRef
10.
go back to reference Smyth MJ, Hayakawa Y, Takeda K, Yagita H (2002) New aspects of natural-killer-cell surveillance and therapy of cancer. Nat Rev Cancer 2:850–861PubMedCrossRef Smyth MJ, Hayakawa Y, Takeda K, Yagita H (2002) New aspects of natural-killer-cell surveillance and therapy of cancer. Nat Rev Cancer 2:850–861PubMedCrossRef
11.
12.
go back to reference Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, Biassoni R, Moretta L (2001) Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223PubMedCrossRef Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, Biassoni R, Moretta L (2001) Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223PubMedCrossRef
13.
go back to reference Moretta L, Bottino C, Pende D, Castriconi R, Mingari MC, Moretta A (2006) Surface NK receptors and their ligands on tumor cells. Semin Immunol 18:151–158PubMedCrossRef Moretta L, Bottino C, Pende D, Castriconi R, Mingari MC, Moretta A (2006) Surface NK receptors and their ligands on tumor cells. Semin Immunol 18:151–158PubMedCrossRef
14.
go back to reference Fukuda M (1991) Lysosomal membrane glycoproteins. Structure, biosynthesis, and intracellular trafficking. J Biol Chem 266:21327–21330PubMed Fukuda M (1991) Lysosomal membrane glycoproteins. Structure, biosynthesis, and intracellular trafficking. J Biol Chem 266:21327–21330PubMed
15.
go back to reference Trapani JA, Smyth MJ (2002) Functional significance of the perforin/granzyme cell death pathway. Nat Rev Immunol 2:735–747PubMedCrossRef Trapani JA, Smyth MJ (2002) Functional significance of the perforin/granzyme cell death pathway. Nat Rev Immunol 2:735–747PubMedCrossRef
16.
go back to reference Van Dommelen SL, Degli-Esposti MA (2004) NKT cells and viral immunity. Immunol Cell Biol 82:332–341PubMedCrossRef Van Dommelen SL, Degli-Esposti MA (2004) NKT cells and viral immunity. Immunol Cell Biol 82:332–341PubMedCrossRef
17.
go back to reference Peralbo E, Alonso C, Solana R (2007) Invariant NKT and NKT-like lymphocytes: two different T cell subsets that are differentially affected by ageing. Exp Gerontol 42:703–708PubMedCrossRef Peralbo E, Alonso C, Solana R (2007) Invariant NKT and NKT-like lymphocytes: two different T cell subsets that are differentially affected by ageing. Exp Gerontol 42:703–708PubMedCrossRef
18.
go back to reference Golden-Mason L, Madrigal-Estebas L, McGrath E, Conroy MJ, Ryan EJ et al (2008) Altered natural killer cell subset distributions in resolved and persistent hepatitis C virus following single source exposure. Gut 57:1121–1128PubMedCrossRef Golden-Mason L, Madrigal-Estebas L, McGrath E, Conroy MJ, Ryan EJ et al (2008) Altered natural killer cell subset distributions in resolved and persistent hepatitis C virus following single source exposure. Gut 57:1121–1128PubMedCrossRef
19.
go back to reference Srivastava R, Aggarwal R, Bhagat MR, Chowdhury A, Naik S (2008) Alterations in natural killer cells and natural killer T cells during acute viral hepatitis E. J Viral Hepat 15:910–916PubMedCrossRef Srivastava R, Aggarwal R, Bhagat MR, Chowdhury A, Naik S (2008) Alterations in natural killer cells and natural killer T cells during acute viral hepatitis E. J Viral Hepat 15:910–916PubMedCrossRef
20.
go back to reference Prabhu SB, Gupta P, Durgapal H, Rath S, Gupta SD et al (2010) Study of cellular immune response against Hepatitis E Virus (HEV). J Viral Hepat 18:587–594PubMedCrossRef Prabhu SB, Gupta P, Durgapal H, Rath S, Gupta SD et al (2010) Study of cellular immune response against Hepatitis E Virus (HEV). J Viral Hepat 18:587–594PubMedCrossRef
21.
go back to reference Arankalle VA, Lole KS, Deshmukh TM, Chobe LP, Gandhe SS (2007) Evaluation of human (genotype-1) and swine (genotype-4)-ORF-2 based ELISAs for anti-HEV IgM and IgG detection in an endemic country and search for type-4human HEV infections. J Viral Hepat 14:435–445PubMedCrossRef Arankalle VA, Lole KS, Deshmukh TM, Chobe LP, Gandhe SS (2007) Evaluation of human (genotype-1) and swine (genotype-4)-ORF-2 based ELISAs for anti-HEV IgM and IgG detection in an endemic country and search for type-4human HEV infections. J Viral Hepat 14:435–445PubMedCrossRef
22.
go back to reference Saravanabalaji S, Tripathy AS, Dhoot RR, Chadha MS, Kakrani AL, Arankalle VA (2009) Viral load, antibody titers and recombinant open reading frame 2 protein- induced TH1/TH2 cytokines and cellular immune responses in self-limiting and fulminant hepatitis E. Intervirology 52:78–85PubMedCrossRef Saravanabalaji S, Tripathy AS, Dhoot RR, Chadha MS, Kakrani AL, Arankalle VA (2009) Viral load, antibody titers and recombinant open reading frame 2 protein- induced TH1/TH2 cytokines and cellular immune responses in self-limiting and fulminant hepatitis E. Intervirology 52:78–85PubMedCrossRef
23.
go back to reference Arankalle VA, Lole KS, Deshmukh TM, Srivastava S, Shaligram US (2009) Challenge studies in Rhesus monkeys immunized with candidate hepatitis E vaccines: DNA, DNA-prime-protein-boost and DNA-protein encapsulated in liposomes. Vaccine 27:1032–1039PubMedCrossRef Arankalle VA, Lole KS, Deshmukh TM, Srivastava S, Shaligram US (2009) Challenge studies in Rhesus monkeys immunized with candidate hepatitis E vaccines: DNA, DNA-prime-protein-boost and DNA-protein encapsulated in liposomes. Vaccine 27:1032–1039PubMedCrossRef
24.
go back to reference Tripathy AS, Das R, Chadha MS, Arankalle VA (2011) Epidemic of Hepatitis B with high mortality in India: association of fulminant disease with lack of CCL4 and natural killer T cells. J Viral Hepat. 18:e415–e422PubMedCrossRef Tripathy AS, Das R, Chadha MS, Arankalle VA (2011) Epidemic of Hepatitis B with high mortality in India: association of fulminant disease with lack of CCL4 and natural killer T cells. J Viral Hepat. 18:e415–e422PubMedCrossRef
25.
go back to reference Das R, Rathod SB, Alagarasu K, Arankalle VA, Tripathy AS (2013) Altered expressions of peripheral CD11c, CD80, CD83 markers and associations of HLA class II allele and haplotypes in self-limiting Hepatitis E infection. Hum Immunol 74:277–285PubMedCrossRef Das R, Rathod SB, Alagarasu K, Arankalle VA, Tripathy AS (2013) Altered expressions of peripheral CD11c, CD80, CD83 markers and associations of HLA class II allele and haplotypes in self-limiting Hepatitis E infection. Hum Immunol 74:277–285PubMedCrossRef
26.
go back to reference Zhao J, Li Y, Jin L, Zhang S, Fan R et al (2012) Natural killer cells are characterized by the concomitantly increased interferon-γ and cytotoxicity in acute resolved hepatitis B patients. PLoS ONE 7:e49135PubMedCrossRefPubMedCentral Zhao J, Li Y, Jin L, Zhang S, Fan R et al (2012) Natural killer cells are characterized by the concomitantly increased interferon-γ and cytotoxicity in acute resolved hepatitis B patients. PLoS ONE 7:e49135PubMedCrossRefPubMedCentral
27.
go back to reference Kakimi K, Guidotti LG, Koezuka Y, Chisari FV (2000) Natural killer T cells activation inhibits hepatitis B virus replication in vivo. J Exp Med 192:921–930PubMedCrossRefPubMedCentral Kakimi K, Guidotti LG, Koezuka Y, Chisari FV (2000) Natural killer T cells activation inhibits hepatitis B virus replication in vivo. J Exp Med 192:921–930PubMedCrossRefPubMedCentral
28.
go back to reference Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, Biassoni R, Moretta L (2001) Activating receptors and coreceptors involved in human natural killer cell-mediate cytolysis. Annu Rev Immunol 19:197–223PubMedCrossRef Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, Biassoni R, Moretta L (2001) Activating receptors and coreceptors involved in human natural killer cell-mediate cytolysis. Annu Rev Immunol 19:197–223PubMedCrossRef
29.
go back to reference Biron CA, Nguyen KB, Pien GC, Cousens LP, Salazar-Mather TP (1999) Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 17:189–220PubMedCrossRef Biron CA, Nguyen KB, Pien GC, Cousens LP, Salazar-Mather TP (1999) Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 17:189–220PubMedCrossRef
30.
go back to reference De Maria A, Biassoni R, Fogli M, Rizzi M, Cantoni C et al (2001) Identification, molecular cloning and functional characterization of NKp46 and NKp30 natural cytotoxicity receptors in Macaca fascicularis NK cells. Eur J Immunol 31:3546–3556PubMedCrossRef De Maria A, Biassoni R, Fogli M, Rizzi M, Cantoni C et al (2001) Identification, molecular cloning and functional characterization of NKp46 and NKp30 natural cytotoxicity receptors in Macaca fascicularis NK cells. Eur J Immunol 31:3546–3556PubMedCrossRef
31.
go back to reference De Maria A, Fogli M, Costa P, Murdaca G, Puppo F et al (2003) The impaired NK cell cytolytic function in viremic HIV-1 infection is associated with a reduced surface expression of natural cytotoxicity receptors (NKp46, NKp30 and NKp44). Eur J Immunol 33:2410–2418PubMedCrossRef De Maria A, Fogli M, Costa P, Murdaca G, Puppo F et al (2003) The impaired NK cell cytolytic function in viremic HIV-1 infection is associated with a reduced surface expression of natural cytotoxicity receptors (NKp46, NKp30 and NKp44). Eur J Immunol 33:2410–2418PubMedCrossRef
32.
go back to reference Fogli M, Costa P, Murdaca G, Setti M, Mingari MC et al (2004) Significant NK cell activation associated with decreased cytolytic function in peripheral blood of HIV-1-infected patients. Eur J Immunol 34:2313–2321PubMedCrossRef Fogli M, Costa P, Murdaca G, Setti M, Mingari MC et al (2004) Significant NK cell activation associated with decreased cytolytic function in peripheral blood of HIV-1-infected patients. Eur J Immunol 34:2313–2321PubMedCrossRef
33.
go back to reference Golden-Mason L, Cox AL, Randall JA, Cheng L, Rosen HR (2010) Increased natural killer cell cytotoxicity and NKp30 expression protects against hepatitis C virus infection in high-risk individuals and inhibits replication in vitro. Hepatology 52:1581–1589PubMedCrossRefPubMedCentral Golden-Mason L, Cox AL, Randall JA, Cheng L, Rosen HR (2010) Increased natural killer cell cytotoxicity and NKp30 expression protects against hepatitis C virus infection in high-risk individuals and inhibits replication in vitro. Hepatology 52:1581–1589PubMedCrossRefPubMedCentral
34.
go back to reference Yoon JC, Lim JB, Park JH, Lee JM (2011) Cell-to-cell contact with hepatitis C virus infected cells reduces functional capacity of natural killer cells. J Virol 85:12557–12569PubMedCrossRefPubMedCentral Yoon JC, Lim JB, Park JH, Lee JM (2011) Cell-to-cell contact with hepatitis C virus infected cells reduces functional capacity of natural killer cells. J Virol 85:12557–12569PubMedCrossRefPubMedCentral
35.
go back to reference Varchetta S, Mele D, Mantovani S, Oliviero B, Cremonesi E et al (2012) Impaired intrahepatic natural killer cell cytotoxic function in chronic hepatitis C virus infection. Hepatology 56:841–849PubMedCrossRef Varchetta S, Mele D, Mantovani S, Oliviero B, Cremonesi E et al (2012) Impaired intrahepatic natural killer cell cytotoxic function in chronic hepatitis C virus infection. Hepatology 56:841–849PubMedCrossRef
36.
go back to reference Pembroke T, Christian A, Jones E, Hills RK, Wang EC et al (2014) The paradox of NKp46 + natural killer cells: drivers of severe hepatitis C virus-induced pathology but in vivo resistance to interferon α treatment. Gut 63:515–524PubMedCrossRefPubMedCentral Pembroke T, Christian A, Jones E, Hills RK, Wang EC et al (2014) The paradox of NKp46 + natural killer cells: drivers of severe hepatitis C virus-induced pathology but in vivo resistance to interferon α treatment. Gut 63:515–524PubMedCrossRefPubMedCentral
37.
go back to reference Mao H, Tu W, Liu Y, Qin G, Zheng J et al (2010) Inhibition of human natural killer cell activity by influenza virions and hemagglutinin. J Virol 84:4148–4157PubMedCrossRefPubMedCentral Mao H, Tu W, Liu Y, Qin G, Zheng J et al (2010) Inhibition of human natural killer cell activity by influenza virions and hemagglutinin. J Virol 84:4148–4157PubMedCrossRefPubMedCentral
38.
go back to reference Krzewski K, Gil-Krzewska A, Nguyen V, Peruzzi G, Coligan JE (2013) LAMP1/CD107a is required for efficient perforin delivery to lytic granules and NK-cell cytotoxicity. Blood 121:4672–4683PubMedCrossRefPubMedCentral Krzewski K, Gil-Krzewska A, Nguyen V, Peruzzi G, Coligan JE (2013) LAMP1/CD107a is required for efficient perforin delivery to lytic granules and NK-cell cytotoxicity. Blood 121:4672–4683PubMedCrossRefPubMedCentral
39.
go back to reference Zhang J, Zhang XF, Zhou C, et al. (2013) Protection against hepatitis E virus infection by naturally acquired and vaccine-induced immunity. Clin Microbiol Infect. doi: 10.1111/1469-0691.12419 Zhang J, Zhang XF, Zhou C, et al. (2013) Protection against hepatitis E virus infection by naturally acquired and vaccine-induced immunity. Clin Microbiol Infect. doi: 10.​1111/​1469-0691.​12419
40.
go back to reference Ralainirina N, Poli A, Michel T, Poos L, Andre`s E, Hentges F, Zimmer J (2007) Control of NK cell functions by CD4+ CD25+ regulatory T cells. J Leuko Biol 81:144–153PubMedCrossRef Ralainirina N, Poli A, Michel T, Poos L, Andre`s E, Hentges F, Zimmer J (2007) Control of NK cell functions by CD4+ CD25+ regulatory T cells. J Leuko Biol 81:144–153PubMedCrossRef
41.
go back to reference Ghiringhelli F, Ménard C, Terme M (2005) CD4+ CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor—dependent manner. J Exp Med 202:1075–1085PubMedCrossRefPubMedCentral Ghiringhelli F, Ménard C, Terme M (2005) CD4+ CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor—dependent manner. J Exp Med 202:1075–1085PubMedCrossRefPubMedCentral
42.
go back to reference Castriconi R, Cantoni C, Della Chiesa M, Vitale M, Marcenaro E et al (2003) Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells. Proc Natl Acad Sci U S A 100:4120–4125PubMedCrossRefPubMedCentral Castriconi R, Cantoni C, Della Chiesa M, Vitale M, Marcenaro E et al (2003) Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells. Proc Natl Acad Sci U S A 100:4120–4125PubMedCrossRefPubMedCentral
43.
go back to reference Rathod SB, Das R, Thanapati S, Arankalle VA, Tripathy AS (2014) Suppressive activity and altered conventional phenotype markers/mediators of regulatory T cells in patients with self-limiting Hepatitis E. J Viral Hepat 21:141–151PubMedCrossRef Rathod SB, Das R, Thanapati S, Arankalle VA, Tripathy AS (2014) Suppressive activity and altered conventional phenotype markers/mediators of regulatory T cells in patients with self-limiting Hepatitis E. J Viral Hepat 21:141–151PubMedCrossRef
Metadata
Title
Increased expressions of NKp44, NKp46 on NK/NKT-like cells are associated with impaired cytolytic function in self-limiting hepatitis E infection
Authors
Rumki Das
Anuradha Tripathy
Publication date
01-10-2014
Publisher
Springer Berlin Heidelberg
Published in
Medical Microbiology and Immunology / Issue 5/2014
Print ISSN: 0300-8584
Electronic ISSN: 1432-1831
DOI
https://doi.org/10.1007/s00430-014-0338-1

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