VCAM-1 and VLA-4 Modulate Dendritic Cell IL-12p40 Production in Experimental Visceral Leishmaniasis

PLoS Pathogens

Jane E. Dalton¹  Paul M. Kaye¹  Asher Maroof¹  Geoff R. Hill²  Wayne A. Schroder²  Fabian Rivera²  Yonghong Zhou²  Amanda C. Stanley²  Susanna H. Rossotti²  Kelli P. MacDonald²  Christian R. Engwerda² 

[1] Immunology and Infection Unit, Department of Biology, University of York, and The Hull York Medical School, York, United Kingdom;Queensland Institute of Medical Research, Herston, Queensland, Australia

关键词: Spleen;    Leishmania donovani;    Parasitic diseases;    T cells;    Cytotoxic T cells;    Macrophages;    Amastigotes;    White blood cells;   

DOI  :  10.1371/journal.ppat.1000158

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY