Functional proteomic analysis for regulatory T cell surveillance of the HIV-1-infected macrophage

Xiuyan Huang, David K. Stone, Fang Yu, Yaoying Zeng, Howard Eliot Gendelman

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Regulatory T cells (Treg) induce robust neuroprotection in murine models of neuroAIDS, in part, through eliciting anti-inflammatory responses for HIV-1-infected brain mononuclear phagocytes (MP; macrophage and microglia). Herein, using both murine and human primary cell cultures in proteomic and cell biologic tests, we report that Treg promotes such neuroprotection by an even broader range of mechanisms than previously seen including inhibition of virus release, killing infected MP, and inducing phenotypic cell switches. Changes in individual Treg-induced macrophage proteins were quantified by iTRAQ labeling followed by mass spectrometry identifications. Reduction in virus release paralleled the upregulation of interferon-stimulated gene 15, an ubiquitin-like protein involved in interferon-mediated antiviral immunity. Treg killed virus-infected macrophages through caspase-3 and granzyme and perforin pathways. Independently, Treg transformed virus-infected macrophages from an M1 to an M2 phenotype by down- and up- regulation of inducible nitric oxide synthase and arginase 1, respectively. Taken together, Treg affects a range of virus-infected MP functions. The observations made serve to challenge the dogma of solitary Treg immune suppressor functions and provides novel insights into how Treg affects adaptive immunosurveillance for control of end organ diseases, notably neurocognitive disorders associated with advanced viral infection.

Original languageEnglish (US)
Pages (from-to)6759-6773
Number of pages15
JournalJournal of Proteome Research
Volume9
Issue number12
DOIs
StatePublished - Dec 3 2010

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T-cells
Macrophages
Regulatory T-Lymphocytes
Viruses
Proteomics
HIV-1
Virus Release
Interferons
Up-Regulation
Ubiquitins
Immunologic Monitoring
Arginase
Granzymes
Perforin
Primary Cell Culture
Microglia
Nitric Oxide Synthase Type II
Virus Diseases
Phagocytes
Caspase 3

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry

Cite this

Functional proteomic analysis for regulatory T cell surveillance of the HIV-1-infected macrophage. / Huang, Xiuyan; Stone, David K.; Yu, Fang; Zeng, Yaoying; Gendelman, Howard Eliot.

In: Journal of Proteome Research, Vol. 9, No. 12, 03.12.2010, p. 6759-6773.

Research output: Contribution to journalArticle

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