SIV infection decreases sympathetic innervation of primate lymph nodes: the role of neurotrophins.
The sympathetic nervous system regulates immune responses in part through direct innervation of lymphoid organs. Recent data indicate that viral infections can alter the structure of lymph node innervation. To determine the molecular mechanisms underlying sympathetic denervation during Simian Immunodeficiency Virus (SIV) infection, we assessed the expression of neurotrophic factors and neuromodulatory cytokines within lymph nodes from experimentally infected rhesus macaques. Transcription of nerve growth factor (NGF), brain-derived neurotropic factor (BDNF) and neurotrophin-4 (NT4) decreased significantly in vivo during chronic SIV infection, whereas expression of the neuro-inhibitory cytokine interferon-gamma (IFN gamma) was up-regulated. Acute SIV infection of macaque leukocytes in vitro induced similar changes in the expression of neurotrophic and neuro-inhibitory factors, indicative of an innate immune response. Statistical mediation analyses of data from in vivo lymph node gene expression suggested that coordinated changes in expression of multiple neuromodulatory factors may contribute to SIV-induced depletion of catecholaminergic varicosities within lymphoid tissue. Given previous evidence that lymph node catecholaminergic varicosities can enhance SIV replication in vivo, these results are consistent with the hypothesis that reduced expression of neurotrophic factors during infection could constitute a neurobiological component of the innate immune response to viral infection.
Sloan
Erica K
EK
University of California Los Angeles, Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine, CA, USA. esloan@ucla.edu
Nguyen
Christina T
CT
Cox
Benjamin F
BF
Tarara
Ross P
RP
Capitanio
John P
JP
Cole
Steve W
SW
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics; D053605:Leukemia Inhibitory Factor / Q000235:genetics; D007962:Leukocytes / Q000276:immunology / Q000821:virology; D008198:Lymph Nodes / Q000294:innervation / Q000502:physiology / Q000821:virology; D008253:Macaca mulatta; D020932:Nerve Growth Factor / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics*; D020933:Neurotrophin 3 / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000503:physiopathology; D015302:Simian Immunodeficiency Virus / Q000254:growth & development / Q000276:immunology*; D013564:Sympathetic Nervous System / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication
D019208:Brain-Derived Neurotrophic Factor; D053605:Leukemia Inhibitory Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D007371:Interferon-gamma; D020932:Nerve Growth Factor; C073922:neurotrophin 4