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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
The human transcriptome during nontyphoid Salmonella and HIV coinfection reveals attenuated NFκB-mediated inflammation and persistent cell cycle disruption
Journal of Infectious Diseases, Volume 204, No. 8, Year 2011
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Description
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. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
Authors & Co-Authors
Schreiber, Fernanda
United Kingdom, Hinxton
Wellcome Sanger Institute
Lynn, David J.
Canada, Burnaby
Simon Fraser University
Canada, Vancouver
The University of British Columbia
Ireland, Dunsany
Grange Research Centre
Houston, Angela Cara
Malawi, Zomba
University of Malawi
Peters, Joanna
Malawi, Zomba
University of Malawi
Mwafulirwa, Gershom
Malawi, Zomba
University of Malawi
Finlay, Barton Brett
Canada, Vancouver
The University of British Columbia
Brinkman, Fiona SL L.
Canada, Burnaby
Simon Fraser University
Hancock, Robert E.W.
Canada, Vancouver
The University of British Columbia
Heyderman, Robert Simon
United Kingdom, Liverpool
University of Liverpool
Malawi, Zomba
University of Malawi
Dougan, Gordon J.
United Kingdom, Hinxton
Wellcome Sanger Institute
Gordon, Melita A.
United Kingdom, Liverpool
University of Liverpool
Malawi, Zomba
University of Malawi
Statistics
Citations: 24
Authors: 11
Affiliations: 6
Identifiers
Doi:
10.1093/infdis/jir512
ISSN:
00221899
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases