TNF Induces Pathogenic Programmed Macrophage Necrosis in Tuberculosis through a Mitochondrial-Lysosomal-Endoplasmic Reticulum Circuit

Roca, Francisco J.; Whitworth, Laura; Redmond, Sarah; Jones, Ana A.; Ramakrishnan, Lalita

doi:10.1016/j.cell.2019.08.004

Cited by 167 publications

(208 citation statements)

References 107 publications

(182 reference statements)

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“…The role of necroptosis, a form of programmed necrotic cell death, remains controversial in TB (Pajuelo et al, 2018;Stutz et al, 2018a;Stutz et al, 2018b;Zhao et al, 2017). TNF-related cell necrosis was reported in Mycobacterium marinum-infected zebrafish in vivo and M. marinum-infected macrophage cell lines in vitro without conforming to the current model of necroptosis (Roca et al, 2019), but that study did not involve Mtb or primary mammalian macrophages. Pyroptosis, a form of programmed necrotic cell death mediated by gasdermin proteins (Kayagaki et al, 2015;Shi et al, 2017;Shi et al, 2015;Wang et al, 2017), usually involves inflammasome activation and the maturation and release of pro-inflammatory cytokines, including IL-1β.…”

Section: Introductionmentioning

confidence: 92%

Type I interferon signaling mediates Mycobacterium tuberculosis–induced macrophage death

Zhang

Jiang

Pfau

et al. 2020

Journal of Experimental Medicine

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Macrophages help defend the host against Mycobacterium tuberculosis (Mtb), the major cause of tuberculosis (TB). Once phagocytized, Mtb resists killing by macrophages, replicates inside them, and leads to their death, releasing Mtb that can infect other cells. We found that the death of Mtb-infected mouse macrophages in vitro does not appear to proceed by a currently known pathway. Through genome-wide CRISPR-Cas9 screening, we identified a critical role for autocrine or paracrine signaling by macrophage-derived type I IFNs in the death of Mtb-infected macrophages in vitro, and blockade of type I IFN signaling augmented the effect of rifampin, a first-line TB drug, in Mtb-infected mice. Further definition of the pathway of type I IFN–mediated macrophage death may allow for host-directed therapy of TB that is more selective than systemic blockade of type I IFN signaling.

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Section: Introductionmentioning

confidence: 92%

Type I interferon signaling mediates Mycobacterium tuberculosis–induced macrophage death

Zhang

Jiang

Pfau

et al. 2020

Journal of Experimental Medicine

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“…Zebrafish has been shown to be an excellent model for the study of TB [21][22][23][24][25] . Because zebrafish have large amounts of offspring at one time and the availability of high throughput automated infection methods 26 , many zebrafish larvae can be tested for TB in a short time.…”

mentioning

confidence: 99%

Tuberculosis causes highly conserved metabolic changes in human patients, mycobacteria-infected mice and zebrafish larvae

Ding

Raterink

Marín-Juez

et al. 2020

Sci Rep

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tuberculosis is a highly infectious and potentially fatal disease accompanied by wasting symptoms, which cause severe metabolic changes in infected people. in this study we have compared the effect of mycobacteria infection on the level of metabolites in blood of humans and mice and whole zebrafish larvae using one highly standardized mass spectrometry pipeline, ensuring technical comparability of the results. Quantification of a range of circulating small amines showed that the levels of the majority of these compounds were significantly decreased in all three groups of infected organisms. Ten of these metabolites were common between the three different organisms comprising: methionine, asparagine, cysteine, threonine, serine, tryptophan, leucine, citrulline, ethanolamine and phenylalanine. The metabolomic changes of zebrafish larvae after infection were confirmed by nuclear magnetic resonance spectroscopy. Our study identified common biomarkers for tuberculosis disease in humans, mice and zebrafish, showing across species conservation of metabolic reprogramming processes as a result of disease. Apparently, the mechanisms underlying these processes are independent of environmental, developmental and vertebrate evolutionary factors. The zebrafish larval model is highly suited to further investigate the mechanism of metabolic reprogramming and the connection with wasting syndrome due to infection by mycobacteria. Infection with Mycobacterium tuberculosis (Mtb) can result in tuberculosis (TB) that currently is newly affecting over 10 million people per year and leading to 1.6 million deaths annually 1. However, the majority of people that have been infected with Mtb, estimated to be in the order of 2 billion, do not experience any symptoms in the presence of positive immunological (blood or skin) test results. In patients diagnosed with TB, the disease is uniformly characterized by a metabolic wasting syndrome that leads to heavy weight loss that concurs with a strong reduction of muscle mass. TB has therefore historically earned the name of "consumption". Novel tools for control of TB should include not only better treatments, including attention to the deleterious effects of wasting syndrome, but also needs to include cost-effective assays for robust and sensitive diagnosis of TB 2. Recent metabolomics studies have identified valuable diagnostic metabolic blood markers that can discriminate TB patients from healthy individuals 3-13. This appeared to be applicable to very different population groups, ranging from trans-Africa, China, Georgia, and Indonesia, and therefore highlighting that blood metabolites are robust and validating biomarkers for TB progression. These studies used mostly mass spectrometry (MS) and

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“…While co-injected recombinant TNF in M. marinum-infected zebrafish larvae initially reduced mycobacterial burden, macrophages underwent necroptosis (programmed necrosis) induced by a RIPK1-RIPK3-dependent mechanism, which in turn enhanced mitochondrial ROS production (64). Exploiting the relative ease of exposing larval zebrafish to chemical inhibitors, it was shown that two pathways cooperate to induce this ROS-dependent macrophage necrosis via an inter-organellar circuit (65). Initially, mitochondrial ROS activates ceramide production via the lysosomal enzyme acid sphingomyelinase (aSM).…”

Section: The Macrophage Response To Mycobacterium Marinum Is Largely mentioning

confidence: 99%

The Diverse Roles of Phagocytes During Bacterial and Fungal Infections and Sterile Inflammation: Lessons From Zebrafish

Linnerz

Hall

2020

Front. Immunol.

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The immediate and natural reaction to both infectious challenges and sterile insults (wounds, tissue trauma or crystal deposition) is an acute inflammatory response. This inflammatory response is mediated by activation of the innate immune system largely comprising professional phagocytes (neutrophils and macrophages). Zebrafish (danio rerio) larvae possess many advantages as a model organism, including their genetic tractability and highly conserved innate immune system. Exploiting these attributes and the live imaging potential of optically transparent zebrafish larvae has greatly contributed to our understanding of how neutrophils and macrophages orchestrate the initiation and resolution phases of inflammatory responses. Numerous bacterial and fungal infection models have been successfully established using zebrafish as an animal model and studies investigating neutrophil and macrophage behavior to sterile insults have also provided unique insights. In this review we highlight how examining the larval zebrafish response to specific bacterial and fungal pathogens has uncovered cellular and molecular mechanisms behind a variety of phagocyte responses, from those that protect the host to those that are detrimental. We also describe how modeling sterile inflammation in larval zebrafish has provided an opportunity to dissect signaling pathways that control the recruitment, and fate, of phagocytes at inflammatory sites. Finally, we briefly discuss some current limitations, and opportunities to improve, the zebrafish model system for studying phagocyte biology.

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TNF Induces Pathogenic Programmed Macrophage Necrosis in Tuberculosis through a Mitochondrial-Lysosomal-Endoplasmic Reticulum Circuit

Cited by 167 publications

References 107 publications

Type I interferon signaling mediates Mycobacterium tuberculosis–induced macrophage death

Type I interferon signaling mediates Mycobacterium tuberculosis–induced macrophage death

Tuberculosis causes highly conserved metabolic changes in human patients, mycobacteria-infected mice and zebrafish larvae

The Diverse Roles of Phagocytes During Bacterial and Fungal Infections and Sterile Inflammation: Lessons From Zebrafish

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