Barclay, R

Brenchley, J

Douek, DC

Estes, JD

Harris, LD

Klatt, NR

Liffson, J

Silvestri, G

Taft, B

Retrovirology

English

PubMed

LD Harris

JD Estes

NR Klatt

B Taft

R Barclay

DC Douek

G Silvestri

J Liffson

J Brenchley

Crossref

BioMed CentralPage 1 of 1(page number not for citation purposes)RetrovirologyOpen AccessPoster presentationP11-01. Extensive intestinal damage underlies microbial translocation in the GI tract of chronically SIV-infected Rhesus macaquesLD Harris*1, JD Estes2, NR Klatt1, B Taft2, R Barclay3, DC Douek4, G Silvestri5, J Liffson2 and J Brenchley1Address: 1Immunopathogenesis Unit, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, MD, USA, 2AIDS and Cancer Virus Program, SAIC, NCI, NIH, Frederick, USA, 3Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK, 4Human Immunology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA and 5Department of Pathology and Laboratory of Medicine, University of Pennsylvania, Philadelphia, PA, USA* Corresponding author    BackgroundActivation of the immune system is a hallmark of thechronic phase of HIV infection and predicts disease pro-gression better than either plasma viral load or CD4 T cellcount. We recently demonstrated that one cause ofimmune activation in chronically HIV-infected humansand chronically SIV-infected rhesus macaques was trans-location of microbial products.MethodsHere, using immuno histochemistry and quantitativeimage analysis, we demonstrate that microbial productstranslocate from the lumen of the intestine into the lam-ina propria and into draining and peripheral lymphnodes.ResultsWe find: 1) microbial products can be found in the lam-ina propria of the large and small bowel and draining anddistal lymph nodes of chronically SIV-infected rhesusmacaques; 2) the mechanisms underlying microbialtranslocation involve breakdown of the tight epithelialbarrier of SIV-infected animals; 3) the degree of epithelialbreakdown correlates with the degree of microbial trans-location; 4) epithelial barrier breakdown and microbialtranslocation begin during the acute phase of infectionand; 5) neither epithelial barrier breakdown nor infiltra-tion of microbial products into the lamina propria occurduring the chronic phase of SIV infection of sooty mang-abeys.ConclusionTaken together, these data provide mechanistic insightunderlying microbial translocation and persistentimmune activation in chronically SIV-infected rhesusmacaques and highlight the importance of understandingthe molecular mechanisms driving this process as a meansto develop therapeutic targets to attenuate chronicimmune activation in HIV-infected individuals.from AIDS Vaccine 2009Paris, France. 19–22 October 2009Published: 22 October 2009Retrovirology 2009, 6(Suppl 3):P146 doi:10.1186/1742-4690-6-S3-P146<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>This abstract is available from: http://www.retrovirology.com/content/6/S3/P146© 2009 Harris et al; licensee BioMed Central Ltd. 

P11-01. Extensive intestinal damage underlies microbial translocation in the GI tract of chronically SIV-infected Rhesus macaques

Harris, Ld

Estes, Jd

Klatt, Nr

Taft, B

Barclay, R

Douek, Dc

Silvestri, G

Liffson, J

Brenchley, J

University of Miami: Scholarship@Miami

Springer - Publisher Connector

BioMed Central
Page 1 of 1
(page number not for citation purposes)
Retrovirology
Open AccessPoster presentation
P11-01. Extensive intestinal damage underlies microbial 
translocation in the GI tract of chronically SIV-infected Rhesus 
macaques
LD Harris*1, JD Estes2, NR Klatt1, B Taft2, R Barclay3, DC Douek4, G Silvestri5, 
J Liffson2 and J Brenchley1
Address: 1Immunopathogenesis Unit, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, MD, USA, 2AIDS and Cancer Virus Program, SAIC, 
NCI, NIH, Frederick, USA, 3Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK, 4Human Immunology Section, Vaccine 
Research Center, NIAID, NIH, Bethesda, MD, USA and 5Department of Pathology and Laboratory of Medicine, University of Pennsylvania, 
Philadelphia, PA, USA
* Corresponding author    
Background
Activation of the immune system is a hallmark of the
chronic phase of HIV infection and predicts disease pro-
gression better than either plasma viral load or CD4 T cell
count. We recently demonstrated that one cause of
immune activation in chronically HIV-infected humans
and chronically SIV-infected rhesus macaques was trans-
location of microbial products.
Methods
Here, using immuno histochemistry and quantitative
image analysis, we demonstrate that microbial products
translocate from the lumen of the intestine into the lam-
ina propria and into draining and peripheral lymph
nodes.
Results
We find: 1) microbial products can be found in the lam-
ina propria of the large and small bowel and draining and
distal lymph nodes of chronically SIV-infected rhesus
macaques; 2) the mechanisms underlying microbial
translocation involve breakdown of the tight epithelial
barrier of SIV-infected animals; 3) the degree of epithelial
breakdown correlates with the degree of microbial trans-
location; 4) epithelial barrier breakdown and microbial
translocation begin during the acute phase of infection
and; 5) neither epithelial barrier breakdown nor infiltra-
tion of microbial products into the lamina propria occur
during the chronic phase of SIV infection of sooty mang-
abeys.
Conclusion
Taken together, these data provide mechanistic insight
underlying microbial translocation and persistent
immune activation in chronically SIV-infected rhesus
macaques and highlight the importance of understanding
the molecular mechanisms driving this process as a means
to develop therapeutic targets to attenuate chronic
immune activation in HIV-infected individuals.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):P146 doi:10.1186/1742-4690-6-S3-P146
<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S3/P146
© 2009 Harris et al; licensee BioMed Central Ltd. 


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P11-01. Extensive intestinal damage underlies microbial translocation in the GI tract of chronically SIV-infected Rhesus macaques

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