THP-1-derived macrophages render lung epithelial cells hypo-responsive to Legionella pneumophila - a systems biology study
Schulz C, Lai X, Bertrams W, Jung AL, Sittka-Stark A, Herkt CE, Janga H, Zscheppang K, Stielow C, Schulte L, Hippenstiel S, Vera J, Schmeck B (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 7
Journal Issue: 1
DOI: 10.1038/s41598-017-12154-4
Abstract
Immune response in the lung has to protect the huge alveolar surface against pathogens while securing the delicate lung structure. Macrophages and alveolar epithelial cells constitute the first line of defense and together orchestrate the initial steps of host defense. In this study, we analysed the influence of macrophages on type II alveolar epithelial cells during Legionella pneumophila-infection by a systems biology approach combining experimental work and mathematical modelling. We found that L. pneumophila-infected THP-1-derived macrophages provoke a pro-inflammatory activation of neighboring lung epithelial cells, but in addition render them hypo-responsive to direct infection with the same pathogen. We generated a kinetic mathematical model of macrophage activation and identified a paracrine mechanism of macrophage-secreted IL-1β inducing a prolonged IRAK-1 degradation in lung epithelial cells. This intercellular crosstalk may help to avoid an overwhelming inflammatory response by preventing excessive local secretion of pro-inflammatory cytokines and thereby negatively regulating the recruitment of immune cells to the site of infection. This suggests an important but ambivalent immunomodulatory role of macrophages in lung infection.
Authors with CRIS profile
Xin Lai
Department of Dermatology
Julio Vera González
Professur für Tumorimmunologie (Schwerpunkt Systembiologie)
Involved external institutions
Justus-Liebig-Universität Gießen
Germany (DE)
Philipps-Universität Marburg
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
Germany (DE)
Philipps-Universität Marburg
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
How to cite
APA:
Schulz, C., Lai, X., Bertrams, W., Jung, A.L., Sittka-Stark, A., Herkt, C.E.,... Schmeck, B. (2017). THP-1-derived macrophages render lung epithelial cells hypo-responsive to Legionella pneumophila - a systems biology study. Scientific Reports, 7(1). https://dx.doi.org/10.1038/s41598-017-12154-4
MLA:
Schulz, Christine, et al. "THP-1-derived macrophages render lung epithelial cells hypo-responsive to Legionella pneumophila - a systems biology study." Scientific Reports 7.1 (2017).
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