Mitochondria in innate immune responses

West, A. Phillip; Shadel, Gerald S.; Ghosh, Sankar

doi:10.1038/nri2975

Cited by 1,128 publications

(1,011 citation statements)

References 102 publications

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“…These metabolic pathways traced to mitochondria. Mitochondria are responsible for initiating and coordinating innate immunity18 and produce stereotyped changes in oxidative metabolism under stress19 that lead to the regulated release of purine and pyrimidine nucleotides like ATP and UTP through cell membrane channels 20. Inside the cell, ATP is an energy carrier.…”

Section: Introductionmentioning

confidence: 99%

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

Naviaux

Curtis

et al. 2017

Ann Clin Transl Neurol

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ObjectiveNo drug is yet approved to treat the core symptoms of autism spectrum disorder (ASD). Low‐dose suramin was effective in the maternal immune activation and Fragile X mouse models of ASD. The Suramin Autism Treatment‐1 (SAT‐1) trial was a double‐blind, placebo‐controlled, translational pilot study to examine the safety and activity of low‐dose suramin in children with ASD.MethodsTen male subjects with ASD, ages 5–14 years, were matched by age, IQ, and autism severity into five pairs, then randomized to receive a single, intravenous infusion of suramin (20 mg/kg) or saline. The primary outcomes were ADOS‐2 comparison scores and Expressive One‐Word Picture Vocabulary Test (EOWPVT). Secondary outcomes were the aberrant behavior checklist, autism treatment evaluation checklist, repetitive behavior questionnaire, and clinical global impression questionnaire.ResultsBlood levels of suramin were 12 ± 1.5 μmol/L (mean ± SD) at 2 days and 1.5 ± 0.5 μmol/L after 6 weeks. The terminal half‐life was 14.7 ± 0.7 days. A self‐limited, asymptomatic rash was seen, but there were no serious adverse events. ADOS‐2 comparison scores improved by −1.6 ± 0.55 points (n = 5; 95% CI = −2.3 to −0.9; Cohen's d = 2.9; P = 0.0028) in the suramin group and did not change in the placebo group. EOWPVT scores did not change. Secondary outcomes also showed improvements in language, social interaction, and decreased restricted or repetitive behaviors.InterpretationThe safety and activity of low‐dose suramin showed promise as a novel approach to treatment of ASD in this small study.

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Section: Introductionmentioning

confidence: 99%

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

Naviaux

Curtis

et al. 2017

Ann Clin Transl Neurol

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“…A recent study has demonstrated that mitochondria participate in a broad range of innate immune pathways, such as the regulation of antiviral signaling and antibacterial immunity, ROS production, autophagy, and cell death. 50 Therefore, it will be interesting to investigate the role of GM-M in host defense against bacterial, viral, and fungal infections in the future.…”

Section: Dv-induced Inflammasome Activation Is Via Clec5amentioning

confidence: 99%

CLEC5A is critical for dengue virus–induced inflammasome activation in human macrophages

Wu¹,

Chen

Yang

et al. 2013

Blood

189

174

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“…Late phagosomes acquire markers such as the lysosomal-associated membrane proteins (LAMP)-1 and -2, which are required for acquisition of Rab7 (9) and of microbicidal properties (10). Crucial to the killing of many intracellular pathogens is the generation of reactive oxygen species (ROS) in the phagosome, which is produced mostly by the NADPH oxidase 2 complex (NOX2) (11,12) and mitochondria (13). The complex, which is normally inactive in the cell, is constituted by six subunits.…”

mentioning

confidence: 99%

Synaptotagmin XI Regulates Phagocytosis and Cytokine Secretion in Macrophages

Duque

Fukuda

Descoteaux

2013

The Journal of Immunology

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Synaptotagmins (Syts) are a group of type I membrane proteins that regulate vesicle docking and fusion in processes such as exocytosis and phagocytosis. All Syts possess a single transmembrane domain, and two conserved tandem Ca2+-binding C2 domains. However, Syts IV and XI possess a conserved serine in their C2A domain that precludes these Syts from binding Ca2+ and phospholipids, and from mediating vesicle fusion. Given the importance of vesicular trafficking in macrophages, we investigated the role of Syt XI in cytokine secretion and phagocytosis. We demonstrated that Syt XI is expressed in murine macrophages, localized in recycling endosomes, lysosomes, and recruited to phagosomes. Syt XI had a direct effect on phagocytosis and on the secretion of TNF and IL-6. Whereas small interfering RNA–mediated knockdown of Syt XI potentiated secretion of these cytokines and particle uptake, overexpression of an Syt XI construct suppressed these processes. In addition, Syt XI knockdown led to decreased recruitment of gp91phox and lysosomal-associated membrane protein–1 to phagosomes, suggesting attenuated microbicidal activity. Remarkably, knockdown of Syt XI ensued in enhanced bacterial survival. Our data reveal a novel role for Syt XI as a regulator of cytokine secretion, particle uptake, and macrophage microbicidal activity.

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Mitochondria in innate immune responses

Cited by 1,128 publications

References 102 publications

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

CLEC5A is critical for dengue virus–induced inflammasome activation in human macrophages

Synaptotagmin XI Regulates Phagocytosis and Cytokine Secretion in Macrophages

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