Inflammation and Taste Disorders

Taste disorders, including taste distortion and taste loss, negatively impact general health and quality of life. To understand the underlying molecular and cellular mechanisms, we set out to identify inflammation‐related molecules in taste tissue and to assess their role in the development of taste dysfunctions. We found that 10 out of 12 mammalian Toll‐like receptors (TLRs), type I and II interferon (IFN) receptors, and their downstream signaling components are present in taste tissue. Some TLRs appear to be selectively or more abundantly expressed in taste buds than in nongustatory lingual epithelium. Immunohistochemistry with antibodies against TLRs 1, 2, 3, 4, 6, and 7 confirmed the presence of these receptor proteins in taste bud cells, of which TLRs 2, 3, and 4 are expressed in the gustducin‐expressing type II taste bud cells. Administration of TLR ligands, lipopolysaccharide, and double‐stranded RNA polyinosinic:polycytidylic acid, which mimics bacterial or viral infection, activates the IFN signaling pathways, upregulates the expression of IFN‐inducible genes, and downregulates the expression of c‐fos in taste buds. Finally, systemic administration of IFNs augments apoptosis of taste bud cells in mice. Taken together, these data suggest that TLR and IFN pathways function collaboratively in recognizing pathogens and mediating inflammatory responses in taste tissue. This process, however, may interfere with normal taste transduction and taste bud cell turnover and contributes to the development of taste disorders.

[1]  Daishu Han,et al.  Expression patterns and functions of toll-like receptors in mouse sertoli cells. , 2008, Endocrinology.

[2]  Hong Wang,et al.  Inflammation Activates the Interferon Signaling Pathways in Taste Bud Cells , 2007, The Journal of Neuroscience.

[3]  T. Owens,et al.  Toll-Like Receptors in Brain Development and Homeostasis , 2007, Science's STKE.

[4]  N. Harpaz,et al.  Enteroendocrine cells express functional Toll-like receptors. , 2007, American journal of physiology. Gastrointestinal and liver physiology.

[5]  K. Fukase,et al.  Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines. , 2007, Molecular immunology.

[6]  T. Hartung,et al.  Membrane Sorting of Toll-like Receptor (TLR)-2/6 and TLR2/1 Heterodimers at the Cell Surface Determines Heterotypic Associations with CD36 and Intracellular Targeting* , 2006, Journal of Biological Chemistry.

[7]  M. Suico,et al.  Membrane-anchored CD14 is required for LPS-induced TLR4 endocytosis in TLR4/MD-2/CD14 overexpressing CHO cells. , 2005, Biochemical and biophysical research communications.

[8]  B. Šakić,et al.  Behavioral effects of infection with interferon-gamma adenovector , 2004, Behavioural Brain Research.

[9]  H. Bourges,et al.  Detection and recognition thresholds to the 4 basic tastes in Mexican patients with primary Sjögren's syndrome , 2004, European Journal of Clinical Nutrition.

[10]  B. Cowart,et al.  Prevalence and Causes of Severe Taste Loss in a Chemosensory Clinic Population , 2003, The Annals of otology, rhinology, and laryngology.

[11]  D. Kalvakolanu,et al.  Alternate interferon signaling pathways. , 2003, Pharmacology & therapeutics.

[12]  P. Garnier,et al.  Ischemic Preconditioning by Caspase Cleavage of Poly(ADP-Ribose) Polymerase-1 , 2003, The Journal of Neuroscience.

[13]  M. Abdollahi,et al.  A review of drug-induced oral reactions. , 2003, The journal of contemporary dental practice.

[14]  Victoria Sherry Taste alterations among patients with cancer. , 2002, Clinical journal of oncology nursing.

[15]  Liquan Huang,et al.  Gγ13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium , 1999, Nature Neuroscience.

[16]  S. Shott,et al.  Taste changes experienced by patients receiving chemotherapy. , 1999, Oncology nursing forum.

[17]  J. Denburg,et al.  Reduced Preference for Sucrose in Autoimmune Mice: A Possible Role of Interleukin-6 , 1997, Brain Research Bulletin.

[18]  J. Ihle Cytokine receptor signalling , 1995, Nature.

[19]  S. Schiffman,et al.  Taste and smell losses in HIV infected patients , 1995, Physiology & Behavior.

[20]  Patrick R. Griffin,et al.  Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis , 1995, Nature.

[21]  P. Fox,et al.  Taste performance in Sjogren's syndrome , 1995, Physiology & Behavior.

[22]  T. Taniguchi,et al.  Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1 , 1994, Cell.

[23]  S. Akira,et al.  Cytokine signal transduction , 1994, Cell.

[24]  S. Harner Peripheral labyrinthine causes of dizziness. , 1987, Postgraduate medicine.

[25]  L. Itri,et al.  Safety and tolerance of recombinant interferon alfa‐2a (roferon®‐A) in Cancer Patients , 1986, Cancer.

[26]  A. Montanaro,et al.  Head and neck manifestations of autoimmune disease. , 1983, American journal of otolaryngology.

[27]  F. R. Smith,et al.  Disordered gustatory acuity in liver disease. , 1976, Gastroenterology.

[28]  R. Henkin,et al.  Hypogeusia, Dysgeusia, Hyposmia, and Dysosmia following Influenza-Like Infection , 1975, The Annals of otology, rhinology, and laryngology.

[29]  L. O’Neill,et al.  Signalling of toll-like receptors. , 2008, Handbook of experimental pharmacology.

[30]  S. Akira,et al.  TLR signaling. , 2006, Current topics in microbiology and immunology.

[31]  B. Beutler,et al.  TYPE I INTERFERONS (/) IN IMMUNITY AND AUTOIMMUNITY , 2005 .

[32]  P. Kellokumpu-Lehtinen,et al.  Combined interferon and vinblastine treatment of advanced melanoma: evaluation of the treatment results and the effects of the treatment on immunological functions , 2004, Cancer Immunology, Immunotherapy.

[33]  S. Estrem,et al.  Disorders of smell and taste. , 1999, The Medical clinics of North America.

[34]  S. Schiffman,et al.  Taste and smell. Neglected senses that contribute to the malnutrition of AIDS. , 1997, North Carolina medical journal.

[35]  J. Gent,et al.  Chemosensory dysfunction. Clinical evaluation results from a taste and smell clinic. , 1987, Postgraduate medicine.