Simian immunodeficiency virus infection alters chemokine networks in lung tissues of cynomolgus macaques: association with Pneumocystis carinii infection.
Infection by HIV-1 frequently leads to pulmonary complications, including alterations to local immune environments. To better understand these alterations, we have examined in detail the patterns and levels of expression of chemokine, cytokine, and chemokine receptor mRNAs in lung tissues from 16 uninfected or simian immunodeficiency virus (SIV)/DeltaB670 infected cynomolgus macaques at different stages of infection. Among the most up-regulated immune genes were interferon (IFN)-gamma, IFN-gamma-inducible CXCR3 ligands, and CCR5 ligands, as well as the cognate chemokine receptors. These changes were greatest in animals with clear Pneumocystis carinii coinfection. Immunohistochemistry and in situ hybridization revealed monocytes/macrophages to be the predominant type of cell infiltrating into lung tissues and serving as the major cellular source of chemokines. To explore the causes of chemokine alterations, we treated macaque lung cells with IFN-gamma, lipopolysaccharide, Poly(I:C), and P. carinii in vitro, and results revealed that these stimuli can induce the expression of CXCR3 ligand and/or CCR5 ligand mRNAs. Taken together, these studies provide a comprehensive definition of the chemokine networks available to modulate cellular recruitment to lung tissues during SIV infection and implicate both cytokines (IFN-gamma) and pathogens (SIV and P. carinii) as contributors to increased expression of pro-inflammatory chemokines.
Qin
Shulin
S
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Fallert Junecko
Beth A
BA
Trichel
Anita M
AM
Tarwater
Patrick M
PM
Murphey-Corb
Michael A
MA
Kirschner
Denise E
DE
Reinhart
Todd A
TA
D000818:Animals; D018925:Chemokines / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008252:Macaca fascicularis; D045363:Pneumocystis carinii / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D019707:Receptors, Chemokine / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D018709:Statistics, Nonparametric
D018925:Chemokines; D019707:Receptors, Chemokine