Transcriptomics

Dataset Information

15

Transcription profiling of human CD14+ peripheral blood monocytes from HIV patients vs uninfected controls suggest that monocyte function is diminished during high-level HIV viremia and that this effect is mediated by chronic stimulation by type I interferons


ABSTRACT: The effect of human immunodeficiency virus (HIV) infection and high-level HIV replication on the function of monocytes was investigated. HIV-positive patients had elevated levels of spontaneous production of some or all of the monocyte proinflammatory cytokines measured (interleukin-1beta [IL-1beta], IL-6, and tumor necrosis factor alpha [TNF-alpha]) compared to uninfected controls. In patients on therapy with high frequencies of monocytes producing proinflammatory cytokines, this frequency was diminished in the context of viremia during an interruption of therapy. Diminished production of proinflammatory cytokines during viremia was restored by culture with autologous CD4(+) T cells or monocytes from an on-therapy time point or lipopolysaccharide (LPS). Microarray analysis demonstrated that diminished monocyte production of proinflammatory cytokines was correlated with elevated type I interferon-stimulated gene transcripts. The addition of exogenous alpha 2A interferon diminished the spontaneous production of IL-1beta, IL-6, and TNF-alpha but did not affect responses to LPS, recapitulating the changes observed for HIV-viremic patients. These results suggest that monocyte function is diminished during high-level HIV viremia and that this effect is mediated by chronic stimulation by type I interferons. This effect on monocytes during viremia may play a role in diminished innate or adaptive immune system functions in HIV-infected patients. In addition, the restoration of these functions may also play a role in some immune reconstitution syndromes observed during initiation of therapy.

ORGANISM(S): Homo sapiens  

DISEASE(S): Viremic Hiv,Aviremic Hiv

SUBMITTER: Richard A. Lempicki  

PROVIDER: E-GEOD-5220 | ArrayExpress | 2007-10-26

SECONDARY ACCESSION(S): GSE5220GDS2168PRJNA96515

REPOSITORIES: GEO, ArrayExpress

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Diminished production of monocyte proinflammatory cytokines during human immunodeficiency virus viremia is mediated by type I interferons.

Tilton John C JC   Johnson Alison J AJ   Luskin Marlise R MR   Manion Maura M MM   Yang Jun J   Adelsberger Joseph W JW   Lempicki Richard A RA   Hallahan Claire W CW   McLaughlin Mary M   Mican Joann M JM   Metcalf Julia A JA   Iyasere Christiana C   Connors Mark M  

Journal of virology 20060927 23


The effect of human immunodeficiency virus (HIV) infection and high-level HIV replication on the function of monocytes was investigated. HIV-positive patients had elevated levels of spontaneous production of some or all of the monocyte proinflammatory cytokines measured (interleukin-1beta [IL-1beta], IL-6, and tumor necrosis factor alpha [TNF-alpha]) compared to uninfected controls. In patients on therapy with high frequencies of monocytes producing proinflammatory cytokines, this frequency was  ...[more]

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