TY - JOUR
T1 - Mycobacteria-host interactions in human bronchiolar airway organoids
AU - Iakobachvili, Nino
AU - Leon-Icaza, Stephen Adonai
AU - Knoops, Kèvin
AU - Sachs, Norman
AU - Mazères, Serge
AU - Simeone, Roxane
AU - Peixoto, Antonio
AU - Bernard, Célia
AU - Murris-Espin, Marlène
AU - Mazières, Julien
AU - Cam, Kaymeuang
AU - Chalut, Christian
AU - Guilhot, Christophe
AU - López-Iglesias, Carmen
AU - Ravelli, Raimond B G
AU - Neyrolles, Olivier
AU - Meunier, Etienne
AU - Lugo-Villarino, Geanncarlo
AU - Clevers, Hans
AU - Cougoule, Céline
AU - Peters, Peter J
N1 - © 2021 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.
PY - 2022/3
Y1 - 2022/3
N2 - Respiratory infections remain a major global health concern. Tuberculosis is one of the top 10 causes of death worldwide, while infections with Non-Tuberculous Mycobacteria are rising globally. Recent advances in human tissue modeling offer a unique opportunity to grow different human "organs" in vitro, including the human airway, that faithfully recapitulates lung architecture and function. Here, we have explored the potential of human airway organoids (AOs) as a novel system in which to assess the very early steps of mycobacterial infection. We reveal that Mycobacterium tuberculosis (Mtb) and Mycobacterium abscessus (Mabs) mainly reside as extracellular bacteria and infect epithelial cells with very low efficiency. While the AO microenvironment was able to control, but not eliminate Mtb, Mabs thrives. We demonstrate that AOs responded to infection by modulating cytokine, antimicrobial peptide, and mucin gene expression. Given the importance of myeloid cells in mycobacterial infection, we co-cultured infected AOs with human monocyte-derived macrophages and found that these cells interact with the organoid epithelium. We conclude that adult stem cell (ASC)-derived AOs can be used to decipher very early events of mycobacteria infection in human settings thus offering new avenues for fundamental and therapeutic research.
AB - Respiratory infections remain a major global health concern. Tuberculosis is one of the top 10 causes of death worldwide, while infections with Non-Tuberculous Mycobacteria are rising globally. Recent advances in human tissue modeling offer a unique opportunity to grow different human "organs" in vitro, including the human airway, that faithfully recapitulates lung architecture and function. Here, we have explored the potential of human airway organoids (AOs) as a novel system in which to assess the very early steps of mycobacterial infection. We reveal that Mycobacterium tuberculosis (Mtb) and Mycobacterium abscessus (Mabs) mainly reside as extracellular bacteria and infect epithelial cells with very low efficiency. While the AO microenvironment was able to control, but not eliminate Mtb, Mabs thrives. We demonstrate that AOs responded to infection by modulating cytokine, antimicrobial peptide, and mucin gene expression. Given the importance of myeloid cells in mycobacterial infection, we co-cultured infected AOs with human monocyte-derived macrophages and found that these cells interact with the organoid epithelium. We conclude that adult stem cell (ASC)-derived AOs can be used to decipher very early events of mycobacteria infection in human settings thus offering new avenues for fundamental and therapeutic research.
U2 - 10.1111/mmi.14824
DO - 10.1111/mmi.14824
M3 - Article
C2 - 34605588
SN - 0950-382X
JO - Molecular Microbiology
JF - Molecular Microbiology
ER -