Transregio SFB-TR 84 “Innate Immunity of the Lung: Mechanisms of Pathogen Attack and Host Defence in Pneumonia“

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Area A

Pathogen recognition in the lung and initiation of innate immune response

 

Area A is dedicated to the investigation of early events in host-pathogen interaction in the lung and addresses consequences of these processes on the signatures of the resulting innate immune response.

Project A1 (Opitz, Diefenbach) dissects the IL-33-ILC3 and IL-22 axis for innate immune activation and alveolar repair in S.p. pneumonia. In project A2 the PIs Wygrecka, Kübler, and Hackstein aim to investigate hitherto unrecognized, coagulation-independent functions of factor FXII during pneumonia. In project A4 (Pillich, Chakraborty, Hippenstiel) the central role of PERK-related signalling with respect to immune activation and lung barrier function will be examined in S.p. infection. A5 (Opitz, Chaput, Heimesaat) uses innovative in vivo models to investigate if and how antibacterial immunity in the lung is influenced systemically by the intestinal microbiota and/or locally by the microbiota of the respiratory tract, and how the impaired IgA production could be restored. Project A6 (Kummer, Diefenbach) follows their observation that NEB cells expressing canonical taste receptors act on BALT formation and remodelling, processes which may be executed by ILC function. A7 (Drosten, Zscheppang) will test how the MERS-CoV protein p4b controls IFN responses and how a single and simple mutation changes its location from the nucleus to the cytosol thereby altering MERS virulence.

Abbreviations: B/Gi-M, Berlin/Gießen-Marburg; B, Berlin; ILC, innate lymphoid cells; rsST2, recombinant soluble ST2 (decoy receptor for IL-33); AMP, antimicrobial peptides; DC, dendritic cell; PMN, polymophonuclear leukocyte; FLNa, filamin A; MVIB, microvilli inclusion body; PLY, pneumolysin; PERK, Protein kinase RNA-like endoplasmic reticulum kinase; chaps, chaperones; asns, asparagine synthetase; TLRlig, Toll-like receptor ligands; MØ, macrophage; P.ae., Pseudomonas aeruginosa; ABiotics, antibiotics;  MERS, Middle East respiratory syndrome coronavirus; RNAseL, ribonuclease L; IFN, interferon; IFNR, interferon receptor; B.pseud., Bordetella pseudohinzii; EC, endothelial cell; TasR, taste receptor; BALT, Bronchus-associated lymphoid tissue; AECs, alveolar epithelial cells, BECs, bronchial epithelial cells. The human figure indicate projects with primary human lung tissue and use of clinical human samples.