Simian immunodeficiency virus dramatically alters expression of homeostatic chemokines and dendritic cell markers during infection in vivo.
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.
Choi
Yang Kyu
YK
Department of Infectious Diseases and Microbiology and the Department of Molecular Genetics and Biochemistry, University of Pittsburgh, PA.
Fallert
Beth A
BA
Murphey-Corb
Michael A
MA
Reinhart
Todd A
TA
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054421:Chemokine CCL21; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D015967:Gene Expression Regulation, Viral; D006706:Homeostasis; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D051907:Lysosomal Membrane Proteins; D008253:Macaca mulatta; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014779:Virus Replication; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000099181:Dectin-1
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054421:Chemokine CCL21; D018925:Chemokines; D019742:Chemokines, CC; D037181:Lectins, C-Type; D051907:Lysosomal Membrane Proteins; D019402:Macrophage Inflammatory Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000099181:Dectin-1; C515460:CCL19 protein, human; C108355:CCL20 protein, human; C515478:CCL21 protein, human; C106311:CCR6 protein, human; C515370:CCR7 protein, human