Characterization of virus-responsive plasmacytoid dendritic cells in the rhesus macaque

Eugene Chung, Sheela B. Amrute, Kristina Abel, Gunjan Gupta, Yichuan Wang, Christopher J. Miller, Patricia Fitzgerald-Bocarsly

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Plasmacytoid dendritic cells (PDC) are potent producers of alpha interferon (IFN-α) in response to enveloped viruses and provide a critical link between the innate and adaptive immune responses. Although the loss of peripheral blood PDC function and numbers has been linked to human immunodeficiency virus (HIV) progression in humans, a suitable animal model is needed to study the effects of immunodeficiency virus infection on PDC function. The rhesus macaque SIV model closely mimics human HIV infection, and recent studies have identified macaque PDC, potentially making the macaque a good model to study PDC regulation. In this study, we demonstrate that peripheral blood PDC from healthy macaques are both phenotypically and functionally similar to human PDC and that reagents used for human studies can be used to study macaque PDC. Both human and macaque PBMC expressed IFN-α in response to herpes simplex virus (HSV), the prototypical activator of PDC, as measured by using an IFN bioassay and IFN-α-specific enzyme-linked immunospot assays. Similar to human PDC, macaque PDC were identified by using flow cytometry as CD123 + HLA-DR+ lineage- cells. In addition, like human PDC, macaque PDC expressed intracellular IFN-α, tumor necrosis factor alpha, macrophage inflammatory protein 1β/CCL4, and IFN-inducible protein 10/CXCL10 upon stimulation with HSV, all as determined by intracellular flow cytometry. We found that IFN regulatory factor 7, which is required for the expression of IFN-α genes, was, similar to human PDC, expressed at high levels in macaque PDC compared to monocytes and CD8+ T cells. These findings establish the phenotypic and functional similarity of human and macaque PDC and confirm the utility of tools developed for studying human PDC in this animal model.

Original languageEnglish (US)
Pages (from-to)426-435
Number of pages10
JournalClinical and Diagnostic Laboratory Immunology
Volume12
Issue number3
DOIs
StatePublished - Mar 1 2005

Fingerprint

Macaca mulatta
Viruses
Dendritic Cells
Macaca
Interferons
Flow cytometry
Virus Diseases
Simplexvirus
Flow Cytometry
Animals
Blood
Animal Models
HIV
Chemokine CXCL10
Macrophage Inflammatory Proteins
Enzyme-Linked Immunospot Assay
T-cells
Bioassay
Adaptive Immunity
HLA-DR Antigens

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

Cite this

Chung, Eugene ; Amrute, Sheela B. ; Abel, Kristina ; Gupta, Gunjan ; Wang, Yichuan ; Miller, Christopher J. ; Fitzgerald-Bocarsly, Patricia. / Characterization of virus-responsive plasmacytoid dendritic cells in the rhesus macaque. In: Clinical and Diagnostic Laboratory Immunology. 2005 ; Vol. 12, No. 3. pp. 426-435.
@article{0df5e015d4a34eb784c554a29aded39f,
title = "Characterization of virus-responsive plasmacytoid dendritic cells in the rhesus macaque",
abstract = "Plasmacytoid dendritic cells (PDC) are potent producers of alpha interferon (IFN-α) in response to enveloped viruses and provide a critical link between the innate and adaptive immune responses. Although the loss of peripheral blood PDC function and numbers has been linked to human immunodeficiency virus (HIV) progression in humans, a suitable animal model is needed to study the effects of immunodeficiency virus infection on PDC function. The rhesus macaque SIV model closely mimics human HIV infection, and recent studies have identified macaque PDC, potentially making the macaque a good model to study PDC regulation. In this study, we demonstrate that peripheral blood PDC from healthy macaques are both phenotypically and functionally similar to human PDC and that reagents used for human studies can be used to study macaque PDC. Both human and macaque PBMC expressed IFN-α in response to herpes simplex virus (HSV), the prototypical activator of PDC, as measured by using an IFN bioassay and IFN-α-specific enzyme-linked immunospot assays. Similar to human PDC, macaque PDC were identified by using flow cytometry as CD123 + HLA-DR+ lineage- cells. In addition, like human PDC, macaque PDC expressed intracellular IFN-α, tumor necrosis factor alpha, macrophage inflammatory protein 1β/CCL4, and IFN-inducible protein 10/CXCL10 upon stimulation with HSV, all as determined by intracellular flow cytometry. We found that IFN regulatory factor 7, which is required for the expression of IFN-α genes, was, similar to human PDC, expressed at high levels in macaque PDC compared to monocytes and CD8+ T cells. These findings establish the phenotypic and functional similarity of human and macaque PDC and confirm the utility of tools developed for studying human PDC in this animal model.",
author = "Eugene Chung and Amrute, {Sheela B.} and Kristina Abel and Gunjan Gupta and Yichuan Wang and Miller, {Christopher J.} and Patricia Fitzgerald-Bocarsly",
year = "2005",
month = "3",
day = "1",
doi = "10.1128/CDLI.12.3.426-435.2005",
language = "English (US)",
volume = "12",
pages = "426--435",
journal = "Clinical and Vaccine Immunology",
issn = "1556-6811",
publisher = "American Society for Microbiology",
number = "3",

}

Characterization of virus-responsive plasmacytoid dendritic cells in the rhesus macaque. / Chung, Eugene; Amrute, Sheela B.; Abel, Kristina; Gupta, Gunjan; Wang, Yichuan; Miller, Christopher J.; Fitzgerald-Bocarsly, Patricia.

In: Clinical and Diagnostic Laboratory Immunology, Vol. 12, No. 3, 01.03.2005, p. 426-435.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Characterization of virus-responsive plasmacytoid dendritic cells in the rhesus macaque

AU - Chung, Eugene

AU - Amrute, Sheela B.

AU - Abel, Kristina

AU - Gupta, Gunjan

AU - Wang, Yichuan

AU - Miller, Christopher J.

AU - Fitzgerald-Bocarsly, Patricia

PY - 2005/3/1

Y1 - 2005/3/1

N2 - Plasmacytoid dendritic cells (PDC) are potent producers of alpha interferon (IFN-α) in response to enveloped viruses and provide a critical link between the innate and adaptive immune responses. Although the loss of peripheral blood PDC function and numbers has been linked to human immunodeficiency virus (HIV) progression in humans, a suitable animal model is needed to study the effects of immunodeficiency virus infection on PDC function. The rhesus macaque SIV model closely mimics human HIV infection, and recent studies have identified macaque PDC, potentially making the macaque a good model to study PDC regulation. In this study, we demonstrate that peripheral blood PDC from healthy macaques are both phenotypically and functionally similar to human PDC and that reagents used for human studies can be used to study macaque PDC. Both human and macaque PBMC expressed IFN-α in response to herpes simplex virus (HSV), the prototypical activator of PDC, as measured by using an IFN bioassay and IFN-α-specific enzyme-linked immunospot assays. Similar to human PDC, macaque PDC were identified by using flow cytometry as CD123 + HLA-DR+ lineage- cells. In addition, like human PDC, macaque PDC expressed intracellular IFN-α, tumor necrosis factor alpha, macrophage inflammatory protein 1β/CCL4, and IFN-inducible protein 10/CXCL10 upon stimulation with HSV, all as determined by intracellular flow cytometry. We found that IFN regulatory factor 7, which is required for the expression of IFN-α genes, was, similar to human PDC, expressed at high levels in macaque PDC compared to monocytes and CD8+ T cells. These findings establish the phenotypic and functional similarity of human and macaque PDC and confirm the utility of tools developed for studying human PDC in this animal model.

AB - Plasmacytoid dendritic cells (PDC) are potent producers of alpha interferon (IFN-α) in response to enveloped viruses and provide a critical link between the innate and adaptive immune responses. Although the loss of peripheral blood PDC function and numbers has been linked to human immunodeficiency virus (HIV) progression in humans, a suitable animal model is needed to study the effects of immunodeficiency virus infection on PDC function. The rhesus macaque SIV model closely mimics human HIV infection, and recent studies have identified macaque PDC, potentially making the macaque a good model to study PDC regulation. In this study, we demonstrate that peripheral blood PDC from healthy macaques are both phenotypically and functionally similar to human PDC and that reagents used for human studies can be used to study macaque PDC. Both human and macaque PBMC expressed IFN-α in response to herpes simplex virus (HSV), the prototypical activator of PDC, as measured by using an IFN bioassay and IFN-α-specific enzyme-linked immunospot assays. Similar to human PDC, macaque PDC were identified by using flow cytometry as CD123 + HLA-DR+ lineage- cells. In addition, like human PDC, macaque PDC expressed intracellular IFN-α, tumor necrosis factor alpha, macrophage inflammatory protein 1β/CCL4, and IFN-inducible protein 10/CXCL10 upon stimulation with HSV, all as determined by intracellular flow cytometry. We found that IFN regulatory factor 7, which is required for the expression of IFN-α genes, was, similar to human PDC, expressed at high levels in macaque PDC compared to monocytes and CD8+ T cells. These findings establish the phenotypic and functional similarity of human and macaque PDC and confirm the utility of tools developed for studying human PDC in this animal model.

UR - http://www.scopus.com/inward/record.url?scp=23844483627&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23844483627&partnerID=8YFLogxK

U2 - 10.1128/CDLI.12.3.426-435.2005

DO - 10.1128/CDLI.12.3.426-435.2005

M3 - Article

C2 - 15753256

AN - SCOPUS:23844483627

VL - 12

SP - 426

EP - 435

JO - Clinical and Vaccine Immunology

JF - Clinical and Vaccine Immunology

SN - 1556-6811

IS - 3

ER -