Pattern recognition receptor responses in children with chronic hepatitis B virus infection

Ida Louise Heiberg; Thilde Nordmann Winther; Søren Riis Paludan; Birthe Hogh

doi:10.1016/j.jcv.2012.04.013

Pattern recognition receptor responses in children with chronic hepatitis B virus infection

Ida Louise Heiberg, Thilde Nordmann Winther, Søren Riis Paludan, Birthe Hogh

Department of Clinical Medicine

9 Citations (Scopus)

Abstract

BACKGROUND: Several studies have demonstrated that hepatitis B virus (HBV) affects the expression and function of Toll like receptors (TLRs), but data on TLR function in HBV infection are mainly from adult patients. The natural history of chronic hepatitis B (CHB) infection is distinctly different in children, since 90% of children become chronic carriers compared to 5% of adults when infected with HBV.

OBJECTIVES: We wanted to study the function of TLRs and cytosolic DNA receptors in children with CHB infection compared to healthy children.

STUDY DESIGN: PBMCs from 19 children with CHB and 19 healthy children were stimulated with ligands for TLR 2, 3, 4, 7 and 9 for 24 h. For activation of cytosolic DNA receptors, cells were transfected with a double-stranded DNA using Lipofectamine 2000. Supernatants were analyzed for levels of IFN-α, TNF-α, IL-6, CXCL10 and CCL3 by Luminex.

RESULTS: Stimulation with ligands for TLR2, TLR3 and TLR9 induced IL-6, CCL3 and CXCL10 to a significantly higher level in children with CHB compared to healthy children. CHB patients displayed significantly lower IFN-α production compared to healthy children after stimulation with ligands for TLR2, TLR3 and TLR4. Stimulation of intracellular DNA sensors with synthetic double-stranded DNA elicited significantly higher induction of the inflammatory cytokines and chemokines IL-6, TNF-α and CCL3 in the CHB patients as compared to the healthy children.

CONCLUSIONS: Our results indicate a TLR-mediated inflammatory response in children with CHB infection. Furthermore, our study is the first to show that the responses of intracellular DNA receptors are affected in CHB.

Original language	English
Journal	Journal of Clinical Virology
Volume	54
Issue number	3
Pages (from-to)	229-34
Number of pages	6
ISSN	1386-6532
DOIs	https://doi.org/10.1016/j.jcv.2012.04.013
Publication status	Published - Jul 2012

Keywords

Adolescent
Cells, Cultured
Child
Child, Preschool
Cytokines/secretion
DNA/immunology
Female
Hepatitis B virus/immunology
Hepatitis B, Chronic/immunology
Humans
Infant
Leukocytes, Mononuclear/immunology
Male
Receptors, Pattern Recognition/immunology
Transfection

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jcv.2012.04.013

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title = "Pattern recognition receptor responses in children with chronic hepatitis B virus infection",

abstract = "BACKGROUND: Several studies have demonstrated that hepatitis B virus (HBV) affects the expression and function of Toll like receptors (TLRs), but data on TLR function in HBV infection are mainly from adult patients. The natural history of chronic hepatitis B (CHB) infection is distinctly different in children, since 90% of children become chronic carriers compared to 5% of adults when infected with HBV.OBJECTIVES: We wanted to study the function of TLRs and cytosolic DNA receptors in children with CHB infection compared to healthy children.STUDY DESIGN: PBMCs from 19 children with CHB and 19 healthy children were stimulated with ligands for TLR 2, 3, 4, 7 and 9 for 24 h. For activation of cytosolic DNA receptors, cells were transfected with a double-stranded DNA using Lipofectamine 2000. Supernatants were analyzed for levels of IFN-α, TNF-α, IL-6, CXCL10 and CCL3 by Luminex.RESULTS: Stimulation with ligands for TLR2, TLR3 and TLR9 induced IL-6, CCL3 and CXCL10 to a significantly higher level in children with CHB compared to healthy children. CHB patients displayed significantly lower IFN-α production compared to healthy children after stimulation with ligands for TLR2, TLR3 and TLR4. Stimulation of intracellular DNA sensors with synthetic double-stranded DNA elicited significantly higher induction of the inflammatory cytokines and chemokines IL-6, TNF-α and CCL3 in the CHB patients as compared to the healthy children.CONCLUSIONS: Our results indicate a TLR-mediated inflammatory response in children with CHB infection. Furthermore, our study is the first to show that the responses of intracellular DNA receptors are affected in CHB.",

keywords = "Adolescent, Cells, Cultured, Child, Child, Preschool, Cytokines/secretion, DNA/immunology, Female, Hepatitis B virus/immunology, Hepatitis B, Chronic/immunology, Humans, Infant, Leukocytes, Mononuclear/immunology, Male, Receptors, Pattern Recognition/immunology, Transfection",

author = "Heiberg, {Ida Louise} and Winther, {Thilde Nordmann} and Paludan, {S{\o}ren Riis} and Birthe Hogh",

year = "2012",

month = jul,

doi = "10.1016/j.jcv.2012.04.013",

language = "English",

volume = "54",

pages = "229--34",

journal = "Journal of Clinical Virology",

issn = "1386-6532",

publisher = "Elsevier",

number = "3",

}

TY - JOUR

T1 - Pattern recognition receptor responses in children with chronic hepatitis B virus infection

AU - Heiberg, Ida Louise

AU - Winther, Thilde Nordmann

AU - Paludan, Søren Riis

AU - Hogh, Birthe

PY - 2012/7

Y1 - 2012/7

N2 - BACKGROUND: Several studies have demonstrated that hepatitis B virus (HBV) affects the expression and function of Toll like receptors (TLRs), but data on TLR function in HBV infection are mainly from adult patients. The natural history of chronic hepatitis B (CHB) infection is distinctly different in children, since 90% of children become chronic carriers compared to 5% of adults when infected with HBV.OBJECTIVES: We wanted to study the function of TLRs and cytosolic DNA receptors in children with CHB infection compared to healthy children.STUDY DESIGN: PBMCs from 19 children with CHB and 19 healthy children were stimulated with ligands for TLR 2, 3, 4, 7 and 9 for 24 h. For activation of cytosolic DNA receptors, cells were transfected with a double-stranded DNA using Lipofectamine 2000. Supernatants were analyzed for levels of IFN-α, TNF-α, IL-6, CXCL10 and CCL3 by Luminex.RESULTS: Stimulation with ligands for TLR2, TLR3 and TLR9 induced IL-6, CCL3 and CXCL10 to a significantly higher level in children with CHB compared to healthy children. CHB patients displayed significantly lower IFN-α production compared to healthy children after stimulation with ligands for TLR2, TLR3 and TLR4. Stimulation of intracellular DNA sensors with synthetic double-stranded DNA elicited significantly higher induction of the inflammatory cytokines and chemokines IL-6, TNF-α and CCL3 in the CHB patients as compared to the healthy children.CONCLUSIONS: Our results indicate a TLR-mediated inflammatory response in children with CHB infection. Furthermore, our study is the first to show that the responses of intracellular DNA receptors are affected in CHB.

AB - BACKGROUND: Several studies have demonstrated that hepatitis B virus (HBV) affects the expression and function of Toll like receptors (TLRs), but data on TLR function in HBV infection are mainly from adult patients. The natural history of chronic hepatitis B (CHB) infection is distinctly different in children, since 90% of children become chronic carriers compared to 5% of adults when infected with HBV.OBJECTIVES: We wanted to study the function of TLRs and cytosolic DNA receptors in children with CHB infection compared to healthy children.STUDY DESIGN: PBMCs from 19 children with CHB and 19 healthy children were stimulated with ligands for TLR 2, 3, 4, 7 and 9 for 24 h. For activation of cytosolic DNA receptors, cells were transfected with a double-stranded DNA using Lipofectamine 2000. Supernatants were analyzed for levels of IFN-α, TNF-α, IL-6, CXCL10 and CCL3 by Luminex.RESULTS: Stimulation with ligands for TLR2, TLR3 and TLR9 induced IL-6, CCL3 and CXCL10 to a significantly higher level in children with CHB compared to healthy children. CHB patients displayed significantly lower IFN-α production compared to healthy children after stimulation with ligands for TLR2, TLR3 and TLR4. Stimulation of intracellular DNA sensors with synthetic double-stranded DNA elicited significantly higher induction of the inflammatory cytokines and chemokines IL-6, TNF-α and CCL3 in the CHB patients as compared to the healthy children.CONCLUSIONS: Our results indicate a TLR-mediated inflammatory response in children with CHB infection. Furthermore, our study is the first to show that the responses of intracellular DNA receptors are affected in CHB.

KW - Adolescent

KW - Cells, Cultured

KW - Child

KW - Child, Preschool

KW - Cytokines/secretion

KW - DNA/immunology

KW - Female

KW - Hepatitis B virus/immunology

KW - Hepatitis B, Chronic/immunology

KW - Humans

KW - Infant

KW - Leukocytes, Mononuclear/immunology

KW - Male

KW - Receptors, Pattern Recognition/immunology

KW - Transfection

U2 - 10.1016/j.jcv.2012.04.013

DO - 10.1016/j.jcv.2012.04.013

M3 - Journal article

C2 - 22579417

SN - 1386-6532

VL - 54

SP - 229

EP - 234

JO - Journal of Clinical Virology

JF - Journal of Clinical Virology

IS - 3

ER -

Pattern recognition receptor responses in children with chronic hepatitis B virus infection

Abstract

Keywords

UN SDGs

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