Airway epithelial cells mount an early response to mycobacterial infection

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

Tom H. M. Ottenhoff¹  Suzanne van Veen¹  Amy M. Barclay¹  Simone A. Joosten¹  Anne M. van der Does²  Pieter S. Hiemstra²  Dennis K. Ninaber² 

[1] Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands;Department of Pulmonology, Leiden University Medical Center, Leiden, Netherlands;

关键词: tuberculosis;    airway epithelium;    host-pathogen interaction;    in vitro;    non-tuberculous mycobacteria;   

DOI  :  10.3389/fcimb.2023.1253037

 received in 2023-07-04, accepted in 2023-08-31,  发布年份 2023

来源: Frontiers

【 摘 要 】

Lung epithelial cells represent the first line of host defence against foreign inhaled components, including respiratory pathogens. Their responses to these exposures may direct subsequent immune activation to these pathogens. The epithelial response to mycobacterial infections is not well characterized and may provide clues to why some mycobacterial infections are cleared, while others are persistent and pathogenic. We have utilized an air-liquid interface model of human primary bronchial epithelial cells (ALI-PBEC) to investigate the epithelial response to infection with a variety of mycobacteria: Mycobacterium tuberculosis (Mtb), M. bovis (BCG), M. avium, and M. smegmatis. Airway epithelial cells were found to be infected by all four species, albeit at low frequencies. The proportion of infected epithelial cells was lowest for Mtb and highest for M. avium. Differential gene expression analysis revealed a common epithelial host response to mycobacteria, including upregulation of BIRC3, S100A8 and DEFB4, and downregulation of BPIFB1 at 48 h post infection. Apical secretions contained predominantly pro-inflammatory cytokines, while basal secretions contained tissue growth factors and chemokines. Finally, we show that neutrophils were attracted to both apical and basal secretions of infected ALI-PBEC. Neutrophils were attracted in high numbers to apical secretions from PBEC infected with all mycobacteria, with the exception of secretions from M. avium-infected ALI-PBEC. Taken together, our results show that airway epithelial cells are differentially infected by mycobacteria, and react rapidly by upregulation of antimicrobials, and increased secretion of inflammatory cytokines and chemokines which directly attract neutrophils. Thus, the airway epithelium may be an important immunological component in controlling and regulating mycobacterial infections.

【 授权许可】

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Copyright © 2023 Barclay, Ninaber, van Veen, Hiemstra, Ottenhoff, van der Does and Joosten