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

Bryan D. Bryson, Tracy R. Rosebrock, Fikadu Tafesse, Christopher Y. Itoh, Armel Nibasumba, Gregory H. Babunovic, Bjorn Corleis, Constance Martin, Caroline Keegan, Priscila Andrade, Susan Realegeno, Douglas Kwon, Robert L. Modlin, Sarah M. Fortune

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number2329
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

tuberculosis
macrophages
Macrophages
Granulocyte-Macrophage Colony-Stimulating Factor
Mycobacterium tuberculosis
Mycobacterium Infections
human immunodeficiency virus
secretions
infectious diseases
Growth
genes
Genes
Cells
HIV
Cytokines
Gene Expression
Survival
cells

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Bryson, B. D., Rosebrock, T. R., Tafesse, F., Itoh, C. Y., Nibasumba, A., Babunovic, G. H., ... Fortune, S. M. (2019). Heterogeneous GM-CSF signaling in macrophages is associated with control of Mycobacterium tuberculosis. Nature communications, 10(1), [2329]. https://doi.org/10.1038/s41467-019-10065-8

Heterogeneous GM-CSF signaling in macrophages is associated with control of Mycobacterium tuberculosis. / Bryson, Bryan D.; Rosebrock, Tracy R.; Tafesse, Fikadu; Itoh, Christopher Y.; Nibasumba, Armel; Babunovic, Gregory H.; Corleis, Bjorn; Martin, Constance; Keegan, Caroline; Andrade, Priscila; Realegeno, Susan; Kwon, Douglas; Modlin, Robert L.; Fortune, Sarah M.

In: Nature communications, Vol. 10, No. 1, 2329, 01.12.2019.

Research output: Contribution to journalArticle

Bryson, BD, Rosebrock, TR, Tafesse, F, Itoh, CY, Nibasumba, A, Babunovic, GH, Corleis, B, Martin, C, Keegan, C, Andrade, P, Realegeno, S, Kwon, D, Modlin, RL & Fortune, SM 2019, 'Heterogeneous GM-CSF signaling in macrophages is associated with control of Mycobacterium tuberculosis', Nature communications, vol. 10, no. 1, 2329. https://doi.org/10.1038/s41467-019-10065-8
Bryson, Bryan D. ; Rosebrock, Tracy R. ; Tafesse, Fikadu ; Itoh, Christopher Y. ; Nibasumba, Armel ; Babunovic, Gregory H. ; Corleis, Bjorn ; Martin, Constance ; Keegan, Caroline ; Andrade, Priscila ; Realegeno, Susan ; Kwon, Douglas ; Modlin, Robert L. ; Fortune, Sarah M. / Heterogeneous GM-CSF signaling in macrophages is associated with control of Mycobacterium tuberculosis. In: Nature communications. 2019 ; Vol. 10, No. 1.
@article{58c362361b974b139ebef924ebf4a7cb,
title = "Heterogeneous GM-CSF signaling in macrophages is associated with control of Mycobacterium tuberculosis",
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.",
author = "Bryson, {Bryan D.} and Rosebrock, {Tracy R.} and Fikadu Tafesse and Itoh, {Christopher Y.} and Armel Nibasumba and Babunovic, {Gregory H.} and Bjorn Corleis and Constance Martin and Caroline Keegan and Priscila Andrade and Susan Realegeno and Douglas Kwon and Modlin, {Robert L.} and Fortune, {Sarah M.}",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41467-019-10065-8",
language = "English (US)",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Heterogeneous GM-CSF signaling in macrophages is associated with control of Mycobacterium tuberculosis

AU - Bryson, Bryan D.

AU - Rosebrock, Tracy R.

AU - Tafesse, Fikadu

AU - Itoh, Christopher Y.

AU - Nibasumba, Armel

AU - Babunovic, Gregory H.

AU - Corleis, Bjorn

AU - Martin, Constance

AU - Keegan, Caroline

AU - Andrade, Priscila

AU - Realegeno, Susan

AU - Kwon, Douglas

AU - Modlin, Robert L.

AU - Fortune, Sarah M.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85066234687&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066234687&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-10065-8

DO - 10.1038/s41467-019-10065-8

M3 - Article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2329

ER -