The human transcriptome during nontyphoid Salmonella and HIV coinfection reveals attenuated NFkappaB-mediated inflammation and persistent cell cycle disruption.
J Infect Dis
; 204(8): 1237-45, 2011 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-21917897
ABSTRACT
BACKGROUND:
Invasive nontyphoid Salmonella (iNTS) disease is common and severe in adults with human immunodeficiency virus (HIV) infection in Africa. We previously observed that ex vivo macrophages from HIV-infected subjects challenged with Salmonella Typhimurium exhibit dysregulated proinflammatory cytokine responses.METHODS:
We studied the transcriptional response in whole blood from HIV-positive patients during acute and convalescent iNTS disease compared to other invasive bacterial diseases, and to HIV-positive and -negative controls.RESULTS:
During iNTS disease, there was a remarkable lack of a coordinated inflammatory or innate immune signaling response. Few interferon γ (IFNγ)-induced genes or Toll-like receptor/transcription factor nuclear factor κB (TLR/NFκB) gene pathways were upregulated in expression. Ex vivo lipopolysacharide (LPS) or flagellin stimulation of whole blood, however, showed that convalescent iNTS subjects and controls were competent to mount prominent TLR/NFκB-associated patterns of mRNA expression. In contrast, HIV-positive patients with other invasive bacterial infections (Escherichia coli and Streptococcus pneumoniae) displayed a pronounced proinflammatory innate immune transcriptional response. There was also upregulated mRNA expression in cell cycle, DNA replication, translation and repair, and viral replication pathways during iNTS. These patterns persisted for up to 2 months into convalescence.CONCLUSIONS:
Attenuation of NFκB-mediated inflammation and dysregulation of cell cycle and DNA-function gene pathway expression are key features of the interplay between iNTS and HIV.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Salmonella
/
Infecções por Salmonella
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Infecções por HIV
/
NF-kappa B
/
HIV
Limite:
Adult
/
Female
/
Humans
/
Male
País/Região como assunto:
Africa
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article