Innate activation of human primary epithelial cells broadens the host response to Mycobacterium tuberculosis in the airways

PLoS Pathogens

Michael R. Edwards¹  Robin J. Shattock²  Corrina Wright³  Sandra M. Newton⁴  Alice Halliday⁵  Nazneen Siddiqui⁵  Samuel Bremang⁵  Ann-Kathrin Reuschl⁵  Robert Parker⁵  Peter Beverley⁵  Ajit Lalvani⁵  Long Hoang⁵  Onn Min Kon⁵  David W. Connell⁵  Hannah Jarvis⁵ 

[1] Department of Cytopathology, Imperial College London, St Mary’s Hospital, Imperial College NHS Trust, London, United Kingdom;Department of Medicine, Imperial College London, St Mary’s Campus, London, United Kingdom;Respiratory Medicine, National Heart and Lung Institute, Imperial College London, St Mary’s Campus, Norfolk Place, London, United Kingdom;Section of Paediatrics, Department of Medicine, St Mary’s Campus, Imperial College, London, United Kingdom;Tuberculosis Research Centre, National Heart and Lung Institute, Imperial College London, St Mary’s Campus, London, United Kingdom

关键词: Mycobacterium tuberculosis;    Epithelial cells;    Gene expression;    Immune response;    Reverse transcriptase-polymerase chain reaction;    Respiratory infections;    Alveolar macrophages;    Interferons;   

DOI  :  10.1371/journal.ppat.1006577

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Early events in the human airways determining whether exposure to Mycobacterium tuberculosis (Mtb) results in acquisition of infection are poorly understood. Epithelial cells are the dominant cell type in the lungs, but little is known about their role in tuberculosis. We hypothesised that human primary airway epithelial cells are part of the first line of defense against Mtb-infection and contribute to the protective host response in the human respiratory tract. We modelled these early airway-interactions with human primary bronchial epithelial cells (PBECs) and alveolar macrophages. By combining in vitro infection and transwell co-culture models with a global transcriptomic approach, we identified PBECs to be inert to direct Mtb-infection, yet to be potent responders within an Mtb-activated immune network, mediated by IL1β and type I interferon (IFN). Activation of PBECs by Mtb-infected alveolar macrophages and monocytes increased expression of known and novel antimycobacterial peptides, defensins and S100-family members and epithelial-myeloid interactions further shaped the immunological environment during Mtb-infection by promoting neutrophil influx. This is the first in depth analysis of the primary epithelial response to infection and offers new insights into their emerging role in tuberculosis through complementing and amplifying responses to Mtb.

【 授权许可】

CC BY