title: Anterior pituitary cells express pattern recognition receptors for fungal glucans: implications for neuroendocrine immune involvement in response to fungal infections.
abstract: OBJECTIVE
  Hormones and cytokines are known to act as regulatory messengers between the neuroendocrine and immune systems. The innate immune system identifies infectious agents by means of pattern-recognition receptors. These receptors recognize pathogen-specific macromolecules called pathogen-associated molecular patterns. Fungal cell wall glucans nonspecifically stimulate various aspects of innate immunity via interaction with membrane receptors on immune-competent cells. Glucans are also released into the systemic circulation of patients with fungal infections. Recent evidence confirms the existence of glucan-specific receptors on cells outside the immune system. We hypothesized that glucans may directly interact with pituitary cells as an early signaling event in fungal infections.
  
  
  METHODS
  We characterized the receptor-mediated interaction of glucan derived from Candida albicans with pituitary cells using surface plasmon resonance. Prolactin levels were assayed by commercial ELISA. TLR2, TLR4 and CD14 mRNA levels were assessed by RT-PCR.
  
  
  RESULTS
  A single glucan-specific binding site was identified on rodent somatomammotroph (K(D) = 3.9 microM) and human folliculostellate cell (K(D) = 3.6 microM) membranes. Coincubation of glucan with somatomammotroph cells for 72 h significantly (p < 0.01) increased prolactin accumulation by 56-62% over that observed in cells treated with media alone. Glucan also increased TLR4 and CD14 gene expression in human folliculostellate cells.
  
  
  CONCLUSIONS
  Pituitary cells directly recognize and respond to fungal cell wall glucans resulting in stimulation of pituitary cell TLR4 and CD14 gene expression. In addition, glucan stimulates secretion of prolactin, a hormone that plays an important role in the response to infection.
authors.affiliation: Department of Obstetrics and Gynecology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA. breuel@etsu.edu
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Breuel
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kougias
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Rice
authors.forename: Duo
authors.initials: D
authors.lastname: Wei
authors.forename: Keith
authors.initials: K
authors.lastname: De Ponti
authors.forename: Jiakun
authors.initials: J
authors.lastname: Wang
authors.forename: John J
authors.initials: JJ
authors.lastname: Laffan
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
authors.forename: John
authors.initials: J
authors.lastname: Kalbfleisch
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000276:immunology; D002176:Candida albicans / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D002473:Cell Wall / Q000276:immunology; D025461:Feedback, Physiological / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D005936:Glucans / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D009181:Mycoses / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000276:immunology*; D009490:Neurosecretory Systems / Q000276:immunology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D005936:Glucans; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D011388:Prolactin