Kliniken & Institute … Institute Zentrum für… Medizinische… Forschung

Immune functions of airway epithelium

We have shown that airway epithelial cells use TLRs for sensing infectious danger. However, TLRs are strictly regulated at mucosal surfaces to avoid overshooting reactions and to account for the specific needs of pathogen recognition in airways. We could show that bronchial epithelial cells regulate local dendritic cells and T-lymphocytes, thereby establishing a specific, tolerogenic microenvironment. We propose a concept of local immunity that is shaped by non-immune, stromal cells. Current research identified constitutive secretion of prostaglandin E2 and glucocorticoids as epithelial mediators that shape the specific microenvironment. Within the SFB938 we analyzed the detailed mechanisms by which non-professional immune cells shape local immune reactivity.
We speculate that additional stressors are necessary to switch from a tolerogenic, homeostatic environment towards a reactive one upon true infection. ER stress was identified to be a kind of “second” signal that mediates this function.
Recent work also focuses on Pseudomonas aeruginosa and its immune-modulatory functions in Cystic Fibrosis.

Selected publications

  1. Platz J, Beisswenger C, Dalpke A, Koczulla R, Pinkenburg O, Vogelmeier C, Bals R (2004): Microbial DNA induces a host defense reaction of human respiratory epithelial cells. J. Immunol. 173 (2): 1219-1223
  2. Mayer AK, Muehmer M, Mages J, Gueinzius K, Hess C, Heeg K, Bals R, Lang R, Dalpke AH (2007): Differential recognition of Toll-like receptor dependant microbial ligands in human bronchial epithelial cells: Implications for pattern recognition at non-sterile mucosal surfaces. J. Immunol. 178(5): 3134-3142
  3. Mayer AK, Bartz H, Fey F, Schmidt L, Dalpke AH (2008). Airway epithelial cells modify innate and adaptive immune responses by inducing an anti-inflammatory microenvironment. Eur J Immunol 38(6): 1689-1699
  4. Schmidt LM, Belvisi MG, Bode KA, Bauer J, Schmidt C, Suchy MT, Tsikas D, Scheuerer J, Lasitschka F, Gröne HJ, Dalpke AH (2011). Bronchial epithelial cell-derived prostaglandin E2 dampens the reactivity of dendritic cells. J Immunol 186(4): 2095-2105
  5. Weitnauer M, Schmidt L, Ng Kuet Leong N, Muenchau S, Lasitschka F, Eckstein V, Hübner S, Tuckermann J and Dalpke AH (2014): Bronchial epithelial cells induce alternatively activated dendritic cells dependent on glucocorticoid receptor signaling. J Immunol, 193(3):1475-84
  6. Oumouna M, Weitnauer M, Mijošek V, Schmidt LM, Eigenbrod T and Dalpke AH (2015): Cell-contact dependent inhibition of monocytes by airway epithelial cells and reversion by infection with Respiratory Syncytial Virus. Immunobiology 220(11): 1240-1245
  7. Weitnauer M, Mijošek V, Dalpke AH (2016): Control of local immunity by airway epithelial cells. Mucosal Immunol. 9: 287-298.
  8. Mijošek V, Lasitschka F, Warth A, Zabeck H, Dalpke AH, Michael Weitnauer (2016): Endoplasmic Reticulum Stress Is a Danger Signal Promoting Innate Inflammatory Responses in Bronchial Epithelial Cells. J Innate Immun; 8(5):464-78.
  9. Ng Kuet Leong N, Brombacher F, Dalpke AH and Weitnauer M (2017): Crosstalk between glucocorticoids and IL-4 modulates Ym1 expression in alternatively activated myeloid cells. Immunobiology 222(5): 759-767.