VCAM-1 and VLA-4 modulate dendritic cell IL-12p40 production in experimental visceral leishmaniasis

Stanley, Amanda C., Dalton, Jane E., Rossotti, Susanna H., MacDonald, Kelli P., Zhou, Yonghong, Rivera, Fabian, Schroder, Wayne A., Maroof, Asher, Hill, Geoff R., Kaye, Paul M. and Engwerda, Christian R. (2008) VCAM-1 and VLA-4 modulate dendritic cell IL-12p40 production in experimental visceral leishmaniasis. PLoS Pathogens, 4 9: e1000158-1-e1000158-11. doi:10.1371/journal.ppat.1000158


Author Stanley, Amanda C.
Dalton, Jane E.
Rossotti, Susanna H.
MacDonald, Kelli P.
Zhou, Yonghong
Rivera, Fabian
Schroder, Wayne A.
Maroof, Asher
Hill, Geoff R.
Kaye, Paul M.
Engwerda, Christian R.
Title VCAM-1 and VLA-4 modulate dendritic cell IL-12p40 production in experimental visceral leishmaniasis
Journal name PLoS Pathogens   Check publisher's open access policy
ISSN 1553-7366
1553-7374
Publication date 2008-09-01
Sub-type Article (original research)
DOI 10.1371/journal.ppat.1000158
Open Access Status DOI
Volume 4
Issue 9
Start page e1000158-1
End page e1000158-11
Total pages 12
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Subject 0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Formatted abstract
Vascular cell adhesion molecule-1 (VCAM-1) interacts with its major ligand very late antigen-4 (VLA-4) to mediate cell adhesion and transendothelial migration of leukocytes. We report an important role for VCAM-1/VLA-4 interactions in the generation of immune responses during experimental visceral leishmaniasis caused by Leishmania donovani. Our studies demonstrate that these molecules play no direct role in the recruitment of leukocytes to the infected liver, but instead contribute to IL-12p40-production by splenic CD8+ dendritic cells (DC). Blockade of VCAM-1/VLA-4 interactions using whole antibody or anti-VCAM-1 Fab´ fragments reduced IL-12p40 mRNA accumulation by splenic DC 5 hours after L. donovani infection. This was associated with reduced anti-parasitic CD4+ T cell activation in the spleen and lowered hepatic IFNγ, TNF and nitric oxide production by 14 days post infection. Importantly, these effects were associated with enhanced parasite growth in the liver in studies with either anti-VCAM-1 or anti-VLA-4 antibodies. These data indicate a role for VCAM-1 and VLA-4 in DC activation during infectious disease.
Copyright: © 2008 Stanley et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keyword Tumor-necrosis-factor
Splenic marginal zone
Donovani infection
Adhesion molecule-1
Acquired resistance
Integrin VLA-4
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Article number: e1000158

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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