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Macrophage Epithelial Reprogramming Underlies Mycobacterial Granuloma Formation and Promotes Infection.

Publication ,  Journal Article
Cronan, MR; Beerman, RW; Rosenberg, AF; Saelens, JW; Johnson, MG; Oehlers, SH; Sisk, DM; Jurcic Smith, KL; Medvitz, NA; Miller, SE; Trinh, LA ...
Published in: Immunity
October 18, 2016

Mycobacterium tuberculosis infection in humans triggers formation of granulomas, which are tightly organized immune cell aggregates that are the central structure of tuberculosis. Infected and uninfected macrophages interdigitate, assuming an altered, flattened appearance. Although pathologists have described these changes for over a century, the molecular and cellular programs underlying this transition are unclear. Here, using the zebrafish-Mycobacterium marinum model, we found that mycobacterial granuloma formation is accompanied by macrophage induction of canonical epithelial molecules and structures. We identified fundamental macrophage reprogramming events that parallel E-cadherin-dependent mesenchymal-epithelial transitions. Macrophage-specific disruption of E-cadherin function resulted in disordered granuloma formation, enhanced immune cell access, decreased bacterial burden, and increased host survival, suggesting that the granuloma can also serve a bacteria-protective role. Granuloma macrophages in humans with tuberculosis were similarly transformed. Thus, during mycobacterial infection, granuloma macrophages are broadly reprogrammed by epithelial modules, and this reprogramming alters the trajectory of infection and the associated immune response.

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Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

October 18, 2016

Volume

45

Issue

4

Start / End Page

861 / 876

Location

United States

Related Subject Headings

  • Zebrafish
  • Mycobacterium tuberculosis
  • Mycobacterium marinum
  • Macrophages
  • Immunology
  • Granuloma
  • Epithelium
  • Cadherins
  • Animals
  • 3204 Immunology
 

Citation

APA
Chicago
ICMJE
MLA
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Cronan, M. R., Beerman, R. W., Rosenberg, A. F., Saelens, J. W., Johnson, M. G., Oehlers, S. H., … Tobin, D. M. (2016). Macrophage Epithelial Reprogramming Underlies Mycobacterial Granuloma Formation and Promotes Infection. Immunity, 45(4), 861–876. https://doi.org/10.1016/j.immuni.2016.09.014
Cronan, Mark R., Rebecca W. Beerman, Allison F. Rosenberg, Joseph W. Saelens, Matthew G. Johnson, Stefan H. Oehlers, Dana M. Sisk, et al. “Macrophage Epithelial Reprogramming Underlies Mycobacterial Granuloma Formation and Promotes Infection.Immunity 45, no. 4 (October 18, 2016): 861–76. https://doi.org/10.1016/j.immuni.2016.09.014.
Cronan MR, Beerman RW, Rosenberg AF, Saelens JW, Johnson MG, Oehlers SH, et al. Macrophage Epithelial Reprogramming Underlies Mycobacterial Granuloma Formation and Promotes Infection. Immunity. 2016 Oct 18;45(4):861–76.
Cronan, Mark R., et al. “Macrophage Epithelial Reprogramming Underlies Mycobacterial Granuloma Formation and Promotes Infection.Immunity, vol. 45, no. 4, Oct. 2016, pp. 861–76. Pubmed, doi:10.1016/j.immuni.2016.09.014.
Cronan MR, Beerman RW, Rosenberg AF, Saelens JW, Johnson MG, Oehlers SH, Sisk DM, Jurcic Smith KL, Medvitz NA, Miller SE, Trinh LA, Fraser SE, Madden JF, Turner J, Stout JE, Lee S, Tobin DM. Macrophage Epithelial Reprogramming Underlies Mycobacterial Granuloma Formation and Promotes Infection. Immunity. 2016 Oct 18;45(4):861–876.
Journal cover image

Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

October 18, 2016

Volume

45

Issue

4

Start / End Page

861 / 876

Location

United States

Related Subject Headings

  • Zebrafish
  • Mycobacterium tuberculosis
  • Mycobacterium marinum
  • Macrophages
  • Immunology
  • Granuloma
  • Epithelium
  • Cadherins
  • Animals
  • 3204 Immunology