| Neisseria gonorrhoeae effectively blocks HIV-1 replication by eliciting a potent TLR9-dependent interferon-α response from plasmacytoid dendritic cells. | |
| | |
MedLine Citation:
|
PMID: 20735437 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
|
Clinical and epidemiological research provides evidence for a positive correlation between Neisseria gonorrhoeae infection and HIV transmission; however, mechanistic studies examining this relationship have yielded conflicting results. To explore this interaction, we exposed ex vivo cultured peripheral blood cells from acute HIV(+) individuals to N. gonorrhoeae. Unexpectedly, we observed a profound inhibition in HIV-1 replication in the ex vivo cultures, and this was recapitulated when peripheral blood mononuclear cells (PBMCs) from healthy donors were co-infected with HIV-1 and N. gonorrhoeae. Next, we established that gonococcal-infected PBMCs liberated a soluble factor that effectively blocked HIV-1 replication. Cytokine analyses and antibody blocking experiments revealed that the type I interferon, interferon-α (IFNα), was expressed upon exposure to N. gonorrhoeae and was responsible for the inhibition of HIV-1. Intracellular staining, TLR9-blocking and cell depletion-based studies demonstrated that the IFNα was elicited by plasmacytoid dendritic cells (pDCs) in a TLR9-dependent manner. The pDC response to N. gonorrhoeae was unexpected given pDCs more established role in innate defence against intracellular pathogens, suggesting this may be a bacterial immune evasion strategy. In the context of HIV, this overcomes the virus's otherwise effective avoidance of the interferon response and represents a previously unrecognized intersection between these two sexually transmitted pathogens. |
| | |
Authors:
|
Wendy N Dobson-Belaire; Anuradha Rebbapragada; Rebecca J Malott; Feng Yun Yue; Colin Kovacs; Rupert Kaul; Mario A Ostrowski; Scott D Gray-Owen |
Related Documents
:
|
16611917 - Hexamethylbisacetamide remodels the human immunodeficiency virus type 1 (hiv-1) promote... 2915387 - Genetic recombination of human immunodeficiency virus. 19239367 - Interleukin-7 receptor signaling is deficient in cd4+ t cells from hiv-infected persons... 8442917 - In vivo decrease in the expression of complement receptor 2 on b-cells in hiv infection. 1204237 - Cryoglobulinaemia in patients with infectious endocarditis. 3480327 - Incidence of anti hiv antibodies and viral antigen in standard and control sera. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Cellular microbiology Volume: 12 ISSN: 1462-5822 ISO Abbreviation: Cell. Microbiol. Publication Date: 2010 Dec |
Date Detail:
|
Created Date: 2010-11-16 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 100883691 Medline TA: Cell Microbiol Country: England |
Other Details:
|
Languages: eng Pagination: 1703-17 Citation Subset: IM |
Copyright Information:
|
© 2010 Blackwell Publishing Ltd. |
Affiliation:
|
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
| Grant Support | |
ID/Acronym/Agency:
|
HET-85518//Canadian Institutes of Health Research |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Epigenetic alteration of the NF-?B-inducing kinase (NIK) gene is involved in enhanced NIK expression...
Next Document: Age-related changes in biological characteristics of human alveolar osteoblasts.