The contribution of the sympathetic nervous system to the immunopathology of experimental pulmonary tuberculosis

The role of norepinephrine (NE) in the immunopathology of experimental tuberculosis (TB) was studied by measuring pulmonary NE and determining its cellular sources and targets. Functional studies were performed administrating adrenergic and anti-adrenergic drugs at different TB phases. Results showed high production of NE during early infection by adrenergic nerve terminals and lymphocytes located in the lungs and mediastinal lymph nodes, these cells highly expressed β2 adreno-receptors (β2AR) which by an autocrine mechanism promote Th-1 cell differentiation favoring protection. During advanced infection, the production of NE and β2AR sharply decreased, suggesting that adrenergic activity is less important during late TB.

[1]  E. Seeley,et al.  Noradrenergic Neurons Regulate Monocyte Trafficking and Mortality during Gram-Negative Peritonitis in Mice , 2013, The Journal of Immunology.

[2]  M. Schwarzschild,et al.  Acute regulation of tyrosine hydroxylase by nerve activity and by neurotransmitters via phosphorylation. , 1989, Annual review of neuroscience.

[3]  I. N. Brown,et al.  Contribution of Th1 and Th2 Cells to Protection and Pathology in Experimental Models of Granulomatous Lung Disease1 , 2001, The Journal of Immunology.

[4]  J. Krueger,et al.  Vagotomy attenuates brain cytokines and sleep induced by peripherally administered tumor necrosis factor-α and lipopolysaccharide in mice. , 2013, Sleep.

[5]  V. Sanders,et al.  IFN-γ Production by Th1 Cells Generated from Naive CD4+ T Cells Exposed to Norepinephrine1 , 2001, The Journal of Immunology.

[6]  G. Rook,et al.  Type 2 cytokine gene activation and its relationship to extent of disease in patients with tuberculosis. , 2000, The Journal of infectious diseases.

[7]  B. Bloom,et al.  Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages , 1992, The Journal of experimental medicine.

[8]  J. Bergquist,et al.  Catecholamines are synthesized by mouse lymphocytes and regulate function of these cells by induction of apoptosis , 1996, Immunology.

[9]  I. Smith,et al.  Immunogenicity and Protection Induced by a Mycobacterium tuberculosissigE Mutant in a BALB/c Mouse Model of Progressive Pulmonary Tuberculosis , 2010, Infection and Immunity.

[10]  R. Straub,et al.  The loss of sympathetic nerve fibers in the synovial tissue of patients with rheumatoid arthritis is accompanied by increased norepinephrine release from synovial macrophages , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[11]  H. Kuhn,et al.  Expression regulation of MAO isoforms in monocytic cells in response to Th2 cytokines. , 2005, Medical science monitor : international medical journal of experimental and clinical research.

[12]  C. Dinarello,et al.  Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones. , 1986, Science.

[13]  A. Sampieri,et al.  Analysis of the local kinetics and localization of interleukin‐1α, tumour necrosis‘qc factor‐α and transforming growth factor‐β, during the course of experimental pulmonary tuberculosis , 1997 .

[14]  J. Polak,et al.  Effect of three animal models of inflammation on nerve fibres in the synovium. , 1994, Annals of the rheumatic diseases.

[15]  S. Felten,et al.  Alterations in cytokine and antibody production following chemical sympathectomy in two strains of mice. , 1995, Journal of immunology.

[16]  K. Madden,et al.  Noradrenergic Sympathetic Neural Interactions with the Immune System: Structure and Function , 1987, Immunological reviews.

[17]  M. Dimitrijević,et al.  Adrenal hormone deprivation affects macrophage catecholamine metabolism and β2‐adrenoceptor density, but not propranolol stimulation of tumour necrosis factor‐α production , 2013, Experimental physiology.

[18]  B. Canning,et al.  Regulation of baseline cholinergic tone in guinea‐pig airway smooth muscle , 1999, The Journal of physiology.

[19]  P. Fadel,et al.  Norepinephrine increases NADPH oxidase-derived superoxide in human peripheral blood mononuclear cells via α-adrenergic receptors. , 2013, American journal of physiology. Regulatory, integrative and comparative physiology.

[20]  G. Rook,et al.  Interactions between hormone‐mediated and vaccine‐mediated immunotherapy for pulmonary tuberculosis in BALB/c mice , 2000, Immunology.

[21]  C. Cavallotti,et al.  Distribution of Catecholaminergic Neurotransmitters and Related Receptors in Human Bronchus-Associated Lymphoid Tissue , 2004, Respiration.

[22]  W. Kummer,et al.  The sensory and sympathetic innervation of guinea-pig lung and trachea as studied by retrograde neuronal tracing and double-labelling immunohistochemistry , 1992, Neuroscience.

[23]  V. Sanders,et al.  Norepinephrine and beta 2-adrenergic receptor stimulation regulate CD4+ T and B lymphocyte function in vitro and in vivo. , 2001, Pharmacological reviews.

[24]  W. Falk,et al.  Soluble neuropilin-2, a nerve repellent receptor, is increased in rheumatoid arthritis synovium and aggravates sympathetic fiber repulsion and arthritis. , 2009, Arthritis and rheumatism.

[25]  R. Palmiter,et al.  Dopamine beta-hydroxylase deficiency impairs cellular immunity. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[26]  A. Sampieri,et al.  Correlation between the kinetics of Th1, Th2 cells and pathology in a murine model of experimental pulmonary tuberculosis. , 1996, Immunology.

[27]  D. Howarth,et al.  Autonomic regulation of lymphatic flow in the lower extremity demonstrated on lymphoscintigraphy in patients with reflex sympathetic dystrophy. , 1999, Clinical nuclear medicine.

[28]  Kevin J. Tracey,et al.  The Neurology of the Immune System: Neural Reflexes Regulate Immunity , 2009, Neuron.

[29]  L. Brunton,et al.  Alpha-adrenergic receptors on rat ventricular myocytes: characteristics and linkage to cAMP metabolism. , 1986, The American journal of physiology.

[30]  G. Rook,et al.  Adrenal changes in murine pulmonary tuberculosis; a clue to pathogenesis? , 1995, FEMS immunology and medical microbiology.

[31]  R. Straub,et al.  The sympathetic nervous response in inflammation , 2014, Arthritis Research & Therapy.

[32]  S. Yoshikawa,et al.  Enhancement of Antimicrobial Activity of Neuropeptide Y by N-Terminal Truncation , 1998, Antimicrobial Agents and Chemotherapy.

[33]  W. Woodward,et al.  Regulation of noradrenergic function by inflammatory cytokines and depolarization , 2003, Journal of neurochemistry.

[34]  D. Bellinger,et al.  Potential use of drugs that target neural-immune pathways in the treatment of rheumatoid arthritis and other autoimmune diseases. , 2003, Current drug targets. Inflammation and allergy.

[35]  A. McGovern,et al.  Characterization of the Vagal Motor Neurons Projecting to the Guinea Pig Airways and Esophagus , 2010, Front. Neur..

[36]  G. Chrousos,et al.  The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. , 1992, JAMA.

[37]  K. Tracey.  Reflex control of immunity , 2009, Nature Reviews Immunology.

[38]  G. Rook,et al.  The pathogenesis of tuberculosis. , 1996, Annual review of microbiology.

[39]  G. Comi,et al.  Interferon-γ and interferon-β affect endogenous catecholamines in human peripheral blood mononuclear cells: Implications for multiple sclerosis , 2005, Journal of Neuroimmunology.

[40]  D. Nance,et al.  Autonomic innervation and regulation of the immune system (1987–2007) , 2007, Brain, Behavior, and Immunity.

[41]  G. Chrousos,et al.  The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. , 2000, Pharmacological reviews.

[42]  Nicholas W. Kin,et al.  It takes nerve to tell T and B cells what to do , 2006, Journal of leukocyte biology.

[43]  Alimuddin Zumla,et al.  Validation of housekeeping genes for normalizing RNA expression in real-time PCR , 2004 .

[44]  H. Togashi,et al.  Enhanced Dendritic Cell Antigen Uptake via α2 Adrenoceptor-Mediated PI3K Activation Following Brief Exposure to Noradrenaline , 2010, The Journal of Immunology.

[45]  Javier Martín,et al.  Lack of validation of genetic variants associated with anti–tumor necrosis factor therapy response in rheumatoid arthritis: a genome-wide association study replication and meta-analysis , 2014, Arthritis Research & Therapy.

[46]  A. McGovern,et al.  Neural regulation of inflammation in the airways and lungs , 2014, Autonomic Neuroscience.

[47]  G. Burnstock.  Cotransmission in the autonomic nervous system. , 2013, Handbook of clinical neurology.

[48]  J. Morales-Montor,et al.  Helminth Infection Alters Mood and Short-Term Memory as well as Levels of Neurotransmitters and Cytokines in the Mouse Hippocampus , 2014, Neuroimmunomodulation.

[49]  L. Swanson,et al.  The organization of noradrenergic pathways from the brainstem to the paraventricular and supraoptic nuclei in the rat , 1982, Brain Research Reviews.