Temporal modulation of host aerobic glycolysis determines the outcome of Mycobacterium marinum infection

Kan, Yuanqing; Meng, Ling; Xie, Lingling; Liu, Lixia; Dong, Wenyue; Feng, Jintao; Yan, Yu-Chen; Zhao, Chao; Peng, Gang; Wang, Decheng; Lu, Mingfang; Yang, Chen; Niu, Chen

doi:10.1016/j.fsi.2019.11.051

Cited by 5 publications

(3 citation statements)

References 43 publications

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“…1 A and Experimental procedures ). RAW 264.7 cells have been used as a model for much of the work studying NFκB signaling dynamics in macrophages ( 19 , 34 , 61 , 62 , 63 , 64 ), gene regulation in pro-inflammatory macrophages ( 65 , 66 , 67 ), and in vitro macrophage models for mycobacterial infection ( 68 , 69 ). The cell line created in our study is heterozygous for the SYFP2 tag at the IRF1 locus and homozygous for both the mCerulean knock-in at the CXCL10 locus and the mCherry knock-in at the CXCL9 locus.…”

Section: Resultsmentioning

confidence: 99%

Quantifying dynamic pro-inflammatory gene expression and heterogeneity in single macrophage cells

Naigles,

Narla,

Soroczynski

et al. 2023

Journal of Biological Chemistry

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Section: Resultsmentioning

confidence: 99%

Quantifying dynamic pro-inflammatory gene expression and heterogeneity in single macrophage cells

Naigles,

Narla,

Soroczynski

et al. 2023

Journal of Biological Chemistry

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“…1A and Methods). RAW264.7 cells have been used as a model for much of the work studying NFkB signaling dynamics in macrophages (19,34,(59)(60)(61)(62), gene regulation in pro-inflammatory macrophages (63)(64)(65), and in vitro macrophage models for mycobacterial infection (66,67). The cell line created in our study is heterozygous for the SYFP2 tag at the IRF1 locus, and homozygous for both the mCerulean knock-in at the CXCL10 locus and the mCherry knock-in at the CXCL9 locus.…”

Section: Quadruple-reporter Macrophage Cell Lines To Study Ifnγ-induc...mentioning

confidence: 99%

Quantifying dynamic pro-inflammatory gene expression and heterogeneity in single macrophage cells

Naigles

Narla

Soroczynski

et al. 2023

Preprint

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Macrophages must respond appropriately to pathogens and other pro-inflammatory stimuli in order to perform their roles in fighting infection. One way in which inflammatory stimuli can vary is in their dynamics - that is, the amplitude and duration of stimulus experienced by the cell. In this study, we performed long-term live cell imaging in a microfluidic device to investigate how the pro-inflammatory genes IRF1, CXCL10, and CXCL9 respond to dynamic interferon-gamma (IFNγ) stimulation. We found that IRF1 responds to low concentration or short duration IFNγ stimulation, whereas CXCL10 and CXCL9 require longer or higher-concentration stimulation to be expressed. We also investigated the heterogeneity in the expression of each gene and found that CXCL10 and CXCL9 have substantial cell-to-cell variability. In particular, the expression of CXCL10 appears to be largely stochastic with a subpopulation of non-responding cells across all the stimulation conditions tested. We developed both deterministic and stochastic models for the expression of each gene. Our modeling analysis revealed that the heterogeneity in CXCL10 can be attributed to a slow chromatin-opening step that is on a similar timescale to that of adaptation of the upstream signal. In this way, CXCL10 expression in individual cells can remain stochastic in response to each pulse of repeated simulations, as validated by experiments. Together, we conclude that pro-inflammatory genes in the same signaling pathway can respond to dynamic IFNγ stimulus with very different response features and that upstream signal adaptation can contribute to shaping the features of heterogeneous gene expression.

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“…Autophagy activation by vitamin D treatment induces autophagy to facilitate antimicrobial function through CAMP production in macrophages infected with M. marinum ( 108 ). In addition, the blockade of glycolysis by inhibitors such as 2-deoxyglucose (2-DG) prior to infection inhibits the proliferation of M. marinum in macrophages and zebrafishes ( 109 ). Thiostrepton (TSR) is an antibiotic harboring a quinaldic acid (QA) moiety that targets bacterial ribosome and induces ER stress-mediated autophagy to promote antimicrobial host defense during M. marinum infection ( 110 ).…”

Section: Autophagy-activating Strategies For Antimicrobial Effects Against Ntm Infectionsmentioning

confidence: 99%

Autophagy and Host Defense in Nontuberculous Mycobacterial Infection

Silwal

Kim

2021

Front. Immunol.

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Autophagy is critically involved in host defense pathways through targeting and elimination of numerous pathogens via autophagic machinery. Nontuberculous mycobacteria (NTMs) are ubiquitous microbes, have become increasingly prevalent, and are emerging as clinically important strains due to drug-resistant issues. Compared to Mycobacterium tuberculosis (Mtb), the causal pathogen for human tuberculosis, the roles of autophagy remain largely uncharacterized in the context of a variety of NTM infections. Compelling evidence suggests that host autophagy activation plays an essential role in the enhancement of antimicrobial immune responses and controlling pathological inflammation against various NTM infections. As similar to Mtb, it is believed that NTM bacteria evolve multiple strategies to manipulate and hijack host autophagy pathways. Despite this, we are just beginning to understand the molecular mechanisms underlying the crosstalk between pathogen and the host autophagy system in a battle with NTM bacteria. In this review, we will explore the function of autophagy, which is involved in shaping host–pathogen interaction and disease outcomes during NTM infections. These efforts will lead to the development of autophagy-based host-directed therapeutics against NTM infection.

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Temporal modulation of host aerobic glycolysis determines the outcome of Mycobacterium marinum infection

Cited by 5 publications

References 43 publications

Quantifying dynamic pro-inflammatory gene expression and heterogeneity in single macrophage cells

Quantifying dynamic pro-inflammatory gene expression and heterogeneity in single macrophage cells

Quantifying dynamic pro-inflammatory gene expression and heterogeneity in single macrophage cells

Autophagy and Host Defense in Nontuberculous Mycobacterial Infection

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