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Heterogeneous GM-CSF signaling in macrophages is associated with control of Mycobacterium tuberculosis

Author

Listed:
  • Bryan D. Bryson

    (Harvard T. H. Chan School of Public Health
    Ragon Institute of MGH, MIT, and Harvard)

  • Tracy R. Rosebrock

    (Harvard T. H. Chan School of Public Health
    Ragon Institute of MGH, MIT, and Harvard)

  • Fikadu G. Tafesse

    (Oregon Health and Science University)

  • Christopher Y. Itoh

    (Harvard T. H. Chan School of Public Health
    Ragon Institute of MGH, MIT, and Harvard)

  • Armel Nibasumba

    (Harvard T. H. Chan School of Public Health
    Ragon Institute of MGH, MIT, and Harvard)

  • Gregory H. Babunovic

    (Harvard T. H. Chan School of Public Health
    Ragon Institute of MGH, MIT, and Harvard)

  • Bjorn Corleis

    (Ragon Institute of MGH, MIT, and Harvard)

  • Constance Martin

    (Harvard T. H. Chan School of Public Health
    Ragon Institute of MGH, MIT, and Harvard)

  • Caroline Keegan

    (David Geffen School of Medicine at University of California)

  • Priscila Andrade

    (David Geffen School of Medicine at University of California)

  • Susan Realegeno

    (David Geffen School of Medicine at University of California)

  • Douglas Kwon

    (Ragon Institute of MGH, MIT, and Harvard)

  • Robert L. Modlin

    (David Geffen School of Medicine at University of California)

  • Sarah M. Fortune

    (Harvard T. H. Chan School of Public Health
    Ragon Institute of MGH, MIT, and Harvard)

Abstract

Variability in bacterial sterilization is a key feature of Mycobacterium tuberculosis (Mtb) disease. In a population of human macrophages, there are macrophages that restrict Mtb growth and those that do not. However, the sources of heterogeneity in macrophage state during Mtb infection are poorly understood. Here, we perform RNAseq on restrictive and permissive macrophages and reveal that the expression of genes involved in GM-CSF signaling discriminates between the two subpopulations. We demonstrate that blocking GM-CSF makes macrophages more permissive of Mtb growth while addition of GM-CSF increases bacterial control. In parallel, we find that the loss of bacterial control that occurs in HIV-Mtb coinfected macrophages correlates with reduced GM-CSF secretion. Treatment of coinfected cells with GM-CSF restores bacterial control. Thus, we leverage the natural variation in macrophage control of Mtb to identify a critical cytokine response for regulating Mtb survival and identify components of the antimicrobial response induced by GM-CSF.

Suggested Citation

  • Bryan D. Bryson & Tracy R. Rosebrock & Fikadu G. Tafesse & Christopher Y. Itoh & Armel Nibasumba & Gregory H. Babunovic & Bjorn Corleis & Constance Martin & Caroline Keegan & Priscila Andrade & Susan , 2019. "Heterogeneous GM-CSF signaling in macrophages is associated with control of Mycobacterium tuberculosis," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10065-8
    DOI: 10.1038/s41467-019-10065-8
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    Cited by:

    1. Rocky Lai & Travis Williams & Tasfia Rakib & Jinhee Lee & Samuel M. Behar, 2024. "Heterogeneity in lung macrophage control of Mycobacterium tuberculosis is modulated by T cells," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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