Innate Immunity to Intracellular Pathogens: Balancing Microbial Elimination and Inflammation

Mitchell, Gabriel; Isberg, Ralph R.

doi:10.1016/j.chom.2017.07.005

Cited by 101 publications

(95 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EVs from M.tb ‐infected macrophages promoted phagosome maturation in M.tb ‐infected macrophages when used as pretreatment agent or after an M.tb infection, leading to reduced mycobacterial replication. Our results also found that EVs from M.tb ‐infected macrophages trigger M.tb ‐containing phagosome maturation through a LC3‐associated pathway . LAP represents an alternative autophagy‐dependent antimicrobial pathway in host cells, where LC3‐modified vesicles fuse with lysosomes, promoting microbial degradation .…”

Section: Discussionsupporting

confidence: 72%

“…Our results also found that EVs from M.tb-infected macrophages trigger M.tb-containing phagosome maturation through a LC3-associated pathway [26]. LAP represents an alternative autophagy-dependent antimicrobial pathway in host cells, where LC3-modified vesicles fuse with lysosomes, promoting microbial degradation [26]. Unlike classical autophagy, LAP is a Ubindependent process and only utilizes a subset of autophagy machinery components for the modification of microbe-containing vesicles by the LC3-conjugation system [27,28].…”

Section: Intra-tracheal Ev Administrationsupporting

confidence: 78%

See 1 more Smart Citation

Extracellular vesicles deliver Mycobacterium RNA to promote host immunity and bacterial killing

Cheng

Schorey

2019

EMBO Reports

View full text Add to dashboard Cite

Extracellular vesicles (EVs) have been shown to carry microbial components and function in the host defense against infections. In this study, we demonstrate that Mycobacterium tuberculosis (M.tb) RNA is delivered into macrophage‐derived EVs through an M.tb SecA2‐dependent pathway and that EVs released from M.tb‐infected macrophages stimulate a host RIG‐I/MAVS/TBK1/IRF3 RNA sensing pathway, leading to type I interferon production in recipient cells. These EVs also promote, in a RIG‐I/MAVS‐dependent manner, the maturation of M.tb‐containing phagosomes through a noncanonical LC3 pathway, leading to increased bacterial killing. Moreover, treatment of M.tb‐infected macrophages or mice with a combination of moxifloxacin and EVs, isolated from M.tb‐infected macrophages, significantly lowered bacterial burden relative to either treatment alone. We hypothesize that EVs, which are preferentially removed by macrophages in vivo, can be combined with effective antibiotics as a novel approach to treat drug‐resistant TB.

show abstract

Section: Discussionsupporting

confidence: 72%

Section: Intra-tracheal Ev Administrationsupporting

confidence: 78%

Extracellular vesicles deliver Mycobacterium RNA to promote host immunity and bacterial killing

Cheng

Schorey

2019

EMBO Reports

View full text Add to dashboard Cite

show abstract

“…Nuclear TFEB activates transcription of autophagy and lysosome genes, and induces autophagosome formation and lysosome biogenesis to upregulate flux through the macro-autophagy pathway. These lysosomal degradative processes generate nutrients that provide energy and support various metabolic functions (reviewed in (98)), and destroy invading organisms in immune cells via the process of xenophagy and enable antigen presentation to mount an immune response (reviewed in (136). …”

Section: Figurementioning

confidence: 99%

Lysosomes Mediate Benefits of Intermittent Fasting in Cardiometabolic Disease: The Janitor Is the Undercover Boss

Mani

Javaheri

Diwan

2018

Comprehensive Physiology

View full text Add to dashboard Cite

Adaptive responses that counter starvation have evolved over millennia to permit organismal survival, including changes at the level of individual organelles, cells, tissues, and organ systems. In the past century, a shift has occurred away from disease caused by insufficient nutrient supply toward overnutrition, leading to obesity and diabetes, atherosclerosis, and cardiometabolic disease. The burden of these diseases has spurred interest in fasting strategies that harness physiological responses to starvation, thus limiting tissue injury during metabolic stress. Insights gained from animal and human studies suggest that intermittent fasting and chronic caloric restriction extend lifespan, decrease risk factors for cardiometabolic and inflammatory disease, limit tissue injury during myocardial stress, and activate a cardioprotective metabolic program. Acute fasting activates autophagy, an intricately orchestrated lysosomal degradative process that sequesters cellular constituents for degradation, and is critical for cardiac homeostasis during fasting. Lysosomes are dynamic cellular organelles that function as incinerators to permit autophagy, as well as degradation of extracellular material internalized by endocytosis, macropinocytosis, and phagocytosis. The last decade has witnessed an explosion of knowledge that has shaped our understanding of lysosomes as central regulators of cellular metabolism and the fasting response. Intriguingly, lysosomes also store nutrients for release during starvation; and function as a nutrient sensing organelle to couple activation of mammalian target of rapamycin to nutrient availability. This article reviews the evidence for how the lysosome, in the guise of a janitor, may be the "undercover boss" directing cellular processes for beneficial effects of intermittent fasting and restoring homeostasis during feast and famine. © 2018 American Physiological Society. Compr Physiol 8:1639-1667, 2018.

show abstract

“…This division can be, however, blurrier as some intravacuolar pathogens, such as S . Typhimurium, can still access the host cytosol …”

Section: Introductionmentioning

confidence: 99%

Sensing of invading pathogens by GBPs: At the crossroads between cell-autonomous and innate immunity

Santos

Brož

2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Guanylate-binding proteins (GBPs) are conserved family of IFN-inducible GTPases that play an important role in the host immunity against bacterial, viral, and protozoan pathogens. GBPs protect the host by associating with intracellular microbes, their vacuolar niche or, in the case of viruses, with their replication complex. This association results in a restriction of the respective pathogen, yet the exact molecular mechanisms of the antimicrobial functions of GBPs are still unclear. Recent work has linked the GBPs with the activation of inflammasomes, multi-protein complexes that assemble upon recognition of pathogen- or host-derived signals and that drive the release of cytokines and host cell death. Here, we will focus on the most recent findings that have started to unravel the manifold restriction mechanism controlled by GBPs in mouse and human cells, and that shed light on the molecular cues that control GBP recruitment to bacterial membranes.

show abstract

Innate Immunity to Intracellular Pathogens: Balancing Microbial Elimination and Inflammation

Cited by 101 publications

References 86 publications

Extracellular vesicles deliver Mycobacterium RNA to promote host immunity and bacterial killing

Extracellular vesicles deliver Mycobacterium RNA to promote host immunity and bacterial killing

Lysosomes Mediate Benefits of Intermittent Fasting in Cardiometabolic Disease: The Janitor Is the Undercover Boss

Sensing of invading pathogens by GBPs: At the crossroads between cell-autonomous and innate immunity

Contact Info

Product

Resources

About