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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-08-2653.

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2002-08-2653v1
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Blood, 1 March 2003, Vol. 101, No. 5, pp. 1684-1691

CHEMOKINES

Simian immunodeficiency virus dramatically alters expression of homeostatic chemokines and dendritic cell markers during infection in vivo

Yang Kyu Choi, Beth A. Fallert, Michael A. Murphey-Corb, and Todd A. Reinhart

From the Department of Infectious Diseases and Microbiology and the Department of Molecular Genetics and Biochemistry, University of Pittsburgh, PA.

Dendritic cells (DCs) are potent antigen-presenting cells that likely play multiple roles in human immunodeficiency virus type 1 (HIV-1) pathogenesis. We used the simian immunodeficiency virus (SIV)/macaque model to study the effects of infection on homeostatic chemokine expression and DC localization directly in secondary lymphoid tissues. SIV infection altered the expression of chemokines (CCL19/MIP-3beta , CCL21/ 6Ckine, and CCL20/MIP-3alpha ) and of chemokine receptors (CCR7 and CCR6) that drive DC trafficking. CCL19/MIP-3beta , CCL20/MIP-3alpha , CCR6, and CCR7 expression increased in lymph nodes during the early systemic burst of viral replication (acute infection), whereas CCL21/6Ckine expression progressively decreased throughout disease to AIDS. Parallel with the SIV-induced perturbations in chemokine expression were changes in the expression of the DC-associated markers, DC-SIGN, DC-LAMP, and DECTIN-1. During AIDS, DC-LAMP mRNA expression levels were significantly reduced in lymph nodes and spleen, and DC-SIGN levels were significantly reduced in spleen. These findings suggest that the disruption of homeostatic chemokine expression is responsible, in part, for alterations in the networks of antigen-presenting cells in lymphoid tissues, ultimately contributing to systemic immunodeficiency.

© 2003 by The American Society of Hematology.
 

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