Increased expression of the inflammatory chemokine CXC chemokine ligand 9/monokine induced by interferon-gamma in lymphoid tissues of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome.
Chemokines are important mediators of cell trafficking during immune inductive and effector activities, and dysregulation of their expression might contribute to the pathogenesis of human immunodeficiency virus type 1 and the related simian immunodeficiency virus (SIV). To understand better the effects of SIV infection on lymphoid tissues in rhesus macaques, we examined chemokine messenger RNA (mRNA) expression patterns by using DNA filter array hybridization. Of the 34 chemokines examined, the interferon gamma (IFN-gamma)-inducible chemokine CXC chemokine ligand 9/monokine induced by interferon-gamma (CXCL9/Mig) was one of the most highly up-regulated chemokines in rhesus macaque spleen tissue early after infection with pathogenic SIV. The relative levels of expression of CXCL9/Mig mRNA in spleen and lymph nodes were significantly increased after infection with SIV in both quantitative image capture and analysis and real-time reverse transcriptase-polymerase chain reaction assays. In addition, in situ hybridization for CXCL9/Mig mRNA revealed that the patterns of expression were altered after SIV infection. Associated with the increased expression of CXCL9/Mig were increased numbers of IFN-gamma mRNA-positive cells in tissues and reduced percentages of CXC chemokine receptor (CXCR) 3(+)/CD3(+) and CXCR3(+)/CD8(+) lymphocytes in peripheral blood. We propose that SIV replication in vivo initiates IFN-gamma-driven positive-feedback loops in lymphoid tissues that disrupt the trafficking of effector T lymphocytes and lead to chronic local inflammation, thereby contributing to immunopathogenesis.
Reinhart
Todd A
TA
Department of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA 15261, USA. reinhar@pitt.edu
Fallert
Beth A
BA
Pfeifer
Melanie E
ME
Sanghavi
Sonali
S
Capuano
Saverio
S
Rajakumar
Premeela
P
Murphey-Corb
Michael
M
Day
Richard
R
Fuller
Craig L
CL
Schaefer
Todd M
TM
D000818:Animals; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D025461:Feedback, Physiological / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism* / Q000473:pathology; D015302:Simian Immunodeficiency Virus; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D014018:Tissue Distribution; D015854:Up-Regulation / Q000276:immunology
C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D007371:Interferon-gamma