Demonstration of spread byMycobacterium tuberculosisbacilli in A549 epithelial cell monolayers

Castro-Garza, Jorge; King, C. Harold; Swords, W. Edward; Quinn, Frederick D.

doi:10.1111/j.1574-6968.2002.tb11258.x

Cited by 43 publications

(23 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this instance, contact of M.tb with ATs is believed to be early and of low frequency. In contrast, contact with ATs may happen at a higher frequency following bacilli release from dying, infected phagocytic cells [7;8] or following release from granulomas [9] (Figure 1A). Recent evidences support that M.tb can invade and replicate within alveolar epithelial type II cells (ATII) during infection [4;7–11].…”

Section: The Role Of the Alveolar Epithelium During Mtb Infectionmentioning

confidence: 99%

Alveolar Epithelial Cells in Mycobacterium tuberculosis Infection: Active Players or Innocent Bystanders?

Scordo

Knoell²,

Torrelles

2015

J Innate Immun

View full text Add to dashboard Cite

Tuberculosis (TB) is a disease that kills one person every 18 s. TB remains a global threat due to the emergence of drug-resistant Mycobacterium tuberculosis (M.tb) strains and the lack of an efficient vaccine. The ability of M.tb to persist in latency, evade recognition following seroconversion, and establish resistance in vulnerable populations warrants closer examination. Past and current research has primarily focused on examination of the role of alveolar macrophages and dendritic cells during M.tb infection, which are critical in the establishment of the host response during infection. However, emerging evidence indicates that the alveolar epithelium is a harbor for M.tb and critical during progression to active disease. Here we evaluate the relatively unexplored role of the alveolar epithelium as a reservoir and also its capacity to secrete soluble mediators upon M.tb exposure, which influence the extent of infection. We further discuss how the M.tb-alveolar epithelium interaction instigates cell-to-cell crosstalk that regulates the immune balance between a proinflammatory and an immunoregulatory state, thereby prohibiting or allowing the establishment of infection. We propose that consideration of alveolar epithelia provides a more comprehensive understanding of the lung environment in vivo in the context of host defense against M.tb.

show abstract

Section: The Role Of the Alveolar Epithelium During Mtb Infectionmentioning

confidence: 99%

Alveolar Epithelial Cells in Mycobacterium tuberculosis Infection: Active Players or Innocent Bystanders?

Scordo

Knoell²,

Torrelles

2015

J Innate Immun

View full text Add to dashboard Cite

show abstract

“…M. marinum and M. tuberculosis can disseminate through release of bacilli following host cell lysis via necrotic or apoptotic cell death (16–18), but studies also document cell-to-cell, antibiotic-insensitive spreading inside an epithelial monolayer (19, 20). M. marinum induces plasma membrane protrusions (2, 9) suggested to participate in dissemination between macrophages in culture (21) and inside zebrafish embryos (22).…”

mentioning

confidence: 99%

Infection by Tubercular Mycobacteria Is Spread by Nonlytic Ejection from Their Amoeba Hosts

Hagedorn

Rohde

Russell

et al. 2009

Science

194

229

View full text Add to dashboard Cite

To generate efficient vaccines and cures for Mycobacterium tuberculosis , we need a far better understanding of its modes of infection, persistence, and spreading. Host cell entry and the establishment of a replication niche are well understood, but little is known about how tubercular mycobacteria exit host cells and disseminate the infection. Using the social amoeba Dictyostelium as a genetically tractable host for pathogenic mycobacteria, we discovered that M. tuberculosis and M. marinum , but not M. avium , are ejected from the cell through an actin-based structure, the ejectosome. This conserved nonlytic spreading mechanism requires a cytoskeleton regulator from the host and an intact mycobacterial ESX-1 secretion system. This insight offers new directions for research into the spreading of tubercular mycobacteria infections in mammalian cells.

show abstract

“…The extensive replication of M. tuberculosis in AECs leads to necrosis and lysis (Dobos et al, 2000;McDonough & Kress, 1995), and subsequent infection of the adjacent AECs (Castro-Garza et al, 2002). Thus, in vivo, M. tuberculosis would replicate in the infected AECs, transform to a disseminative phenotype, lyse the cells, spread to adjacent cells and continue to replicate/ lyse, simultaneously disseminating systemically to achieve widespread infection before adaptive immune responses that induce latency are elicited (Wolf et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Understanding dissemination of Mycobacterium tuberculosis from the lungs during primary infection

Ryndak

Chandra

Laal

2016

Journal of Medical Microbiology

View full text Add to dashboard Cite

Understanding how inhaled Mycobacterium tuberculosis achieves dramatic replication and crosses the alveolar barrier to establish systemic latent infection, before adaptive immunity is elicited in humans, is limited by the small infecting inoculum carried in aerosol droplets (1-5 mm diameter) and the inability to identify the time of infection. M. tuberculosis is believed to disseminate via infected macrophages. However, like other invasive bacterial pathogens, M. tuberculosis could also cross the barrier directly using adhesins and toxins. An in vitro alveolar barrier mimicking the gas-exchange regions of the alveolus was devised comprising monolayers of human alveolar epithelial and endothelial cells cultured on opposing sides of a basement membrane. Migration of dissemination-competent strains of M. tuberculosis, and dissemination-attenuated M. tuberculosis and Mycobacterium bovis mutant strains lacking adhesin/toxin ESAT-6 and adhesin HBHA were tested for macrophage-free migration across the barrier. Strains that disseminate similarly in vivo migrated similarly across the in vitro alveolar barrier. Strains lacking ESAT-6 expression/secretion were attenuated, and absence of both ESAT-6 and HBHA increased attenuation of bacterial migration across the barrier. Thus, as reported for other bacteria, M. tuberculosis utilizes adhesins and toxins for macrophageindependent crossing of the alveolar barrier. This in vitro model will allow identification and characterization of molecules/mechanisms employed by M. tuberculosis to establish systemic latent tuberculosis infection during primary infection.

show abstract

Demonstration of spread byMycobacterium tuberculosisbacilli in A549 epithelial cell monolayers

Cited by 43 publications

References 20 publications

Alveolar Epithelial Cells in <b><i>Mycobacterium tuberculosis</i></b> Infection: Active Players or Innocent Bystanders?

Alveolar Epithelial Cells in <b><i>Mycobacterium tuberculosis</i></b> Infection: Active Players or Innocent Bystanders?

Infection by Tubercular Mycobacteria Is Spread by Nonlytic Ejection from Their Amoeba Hosts

Understanding dissemination of Mycobacterium tuberculosis from the lungs during primary infection

Contact Info

Product

Resources

About