Simian Immunodeficiency Virus Infection Potently Modulates Chemokine Networks and Immune Environments in Hilar Lymph Nodes of Cynomolgus Macaques

Qin, Shulin MD, PhD*; Junecko, Beth A.F. BS*; Lucero, Carissa M. MPH*; Klamar, Cynthia R. MS*; Trichel, Anita M. DVM, PhD; Murphey-Corb, Michael A. PhD; Tarwater, Patrick M. PhD; Kirschner, Denise E. PhD§; Reinhart, Todd A. ScD*

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e31828ac85f
Basic and Translational Science
Abstract

Background: Chemokines provide critical immune cell homing and activation signals that if altered could affect the inflammatory milieu and cellular composition of lymphoid tissues. During HIV-1 and simian immunodeficiency virus (SIV)–infection, the virus triggers an increase in inflammation or activation, leading to immunodeficiency and development of opportunistic infections, such as in the lungs—a massive interface between the host and the environment.

Methods: Chemokine, cytokine, and chemokine receptor expression profiles were determined using real-time reverse transcriptase—polymerase chain reaction and in situ hybridization in hilar lymph nodes (HiLNs) from cynomolgus macaques at different stages after infection with SIV/DeltaB670. Immunostaining of tissue sections and flow cytometric analysis of cryopreserved cells were used to examine cellular compositions of lymph nodes.

Results: Interferon-gamma, type 1 chemokine, and cognate chemokine receptor mRNAs were upregulated, whereas type 2 and homeostatic chemokine and chemokine receptor mRNAs were down-regulated in HiLNs after SIV infection. Local SIV and interferon-gamma levels were positively correlated with type 1 chemokine levels but negatively correlated with type 2 and homeostatic chemokine levels. Using in situ hybridization, Pneumocystis carinii rRNA was detected in lung-draining lymph nodes from animals with P. carinii pneumonia. Changes in the cellular composition of HiLNs included decreased proportions of CD4+ cells and dendritic cells and increased proportions of CD8+, CXCR3+, and CCR5+ cells.

Conclusions: SIV infection of cynomolgus macaques dramatically alters the cellular homing signals of lung-draining lymph nodes, which correlated with changes in the immune cellular composition. These changes could contribute to the loss of immune function that defines AIDS.

Author Information

*Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA;

Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pittsburgh, PA;

Division of Biostatistics & Epidemiology, Texas Tech University Health Science Center, El Paso, TX; and

§Department of Microbiology & Immunology, University of Michigan, Ann Arbor, MI.

Correspondence to: Todd A. Reinhart, ScD, Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 606 Parran Hall, 130 DeSoto Street, Pittsburgh, PA 15261 (e-mail: reinhar@pitt.edu).

Supported by the National Institute of Health Grants RO1 HL072682 (to D. E. Kirschner) and RO1 AI060422 (to T. A. Reinhart).

The authors have no conflicts of interest to disclose.

T. A. R., S. Q., and D. E. K. conceived and designed the experiments; S. Q., B. A. F. J., C. M. L., C. R. K., A. M. T., and M. A. M.-C. performed the experiments; S. Q., T. A. R., and P. M. T. analyzed the data; S. Q. and T. A. R. wrote the article; B. A. F. J., A. M. T., D. E. K., P. M. T., and M. A. M.-C. critically reviewed the article.

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Received July 28, 2012

Accepted January 30, 2013

© 2013 by Lippincott Williams & Wilkins