Innate and adaptive effects of inflammasomes on T cell responses

Dostert, Catherine; Ludigs, Kristina; Guarda, Greta

doi:10.1016/j.coi.2013.02.008

Cited by 38 publications

(22 citation statements)

References 56 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, inflammasome activation promotes T-cell responses. 39 Recent studies in rodent and human suggest that the NLRP3 inflammasome and T-helper 1 cell shift in the T-cell population in adipose tissue contribute to inflammation and insulin resistance. 40 The effect of NR-mediated inhibition of NLRP3 inflammasome activation on T cell and other inflammatory factors will be interesting to study.…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes

Lee

Hong

Jun

et al. 2015

Journal of Medicinal Food

View full text Add to dashboard Cite

Low-grade chronic inflammation (metaflammation) is a major contributing factor for the onset and development of metabolic diseases, such as type 2 diabetes, obesity, and cardiovascular disease. Nicotinamide riboside (NR), which is present in milk and beer, is a functional vitamin B3 having advantageous effects on metabolic regulation. However, the anti-inflammatory capacity of NR is unknown. This study evaluated whether NR modulates hepatic nucleotide binding and oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Male, 8-week-old KK/HlJ mice were allocated to the control or NR group. NR (100 mg/kg/day) or vehicle (phosphate-buffered saline) was administrated by an osmotic pump for 7 days. Glucose control, lipid profiles, NLRP3 inflammasome, and inflammation markers were analyzed, and structural and histological analyses were conducted. NR treatment did not affect body weight gain, food intake, and liver function. Glucose control based on the oral glucose tolerance test and levels of serum insulin and adiponectin was improved by NR treatment. Among tested lipid profiles, NR lowered the total cholesterol concentration in the liver. Histological and structural analysis by hematoxylin and eosin staining and transmission electron microscopy, respectively, showed that NR rescued the disrupted cellular integrity of the mitochondria and nucleus in the livers of obese and diabetic KK mice. In addition, NR treatment significantly improved hepatic proinflammatory markers, including tumor necrosis factor-alpha, interleukin (IL)-6, and IL-1. These ameliorations were accompanied by significant shifts of NLRP3 inflammasome components (NLRP3, ASC, and caspase1). These results demonstrate that NR attenuates hepatic metaflammation by modulating the NLRP3 inflammasome.

show abstract

Section: Discussionmentioning

confidence: 99%

Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes

Lee

Hong

Jun

et al. 2015

Journal of Medicinal Food

View full text Add to dashboard Cite

show abstract

“…Emerging evidence has suggested that inflammasome pathway can influence or modulate host adaptive immune responses in infection and immunization (53–55). For examples, IL-1β and IL-18 are key cytokines that not only activate monocytes, macrophages and neutrophils but have also been shown to drive the development of CD4 T-cell response (54, 56) and antibody response (57, 58).…”

Section: Discussionmentioning

confidence: 99%

Priming and Activation of Inflammasome by Canarypox Virus Vector ALVAC via the cGAS/IFI16–STING–Type I IFN Pathway and AIM2 Sensor

Liu

Niu

Fan

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

Viral vectors derived from different virus families, including poxvirus (canarypox virus vector ALVAC) and adenovirus (human Ad5 vector), have been widely used in vaccine development for a range of human diseases including HIV/AIDS. Less is known about mechanisms underlying host innate response to these vectors. Increasing evidence from clinical vaccine trials testing different viral vectors has suggested the importance of understanding basic elements of host-viral vector interactions. In this study, we investigated the innate interactions of antigen presenting cells (APCs) with two commonly used HIV vaccine vectors, ALVAC and Ad5, and herein reported identification of AIM2 as an innate sensor for ALVAC triggering strong inflammasome activation in both human and mouse APCs. Microarray and comprehensive gene knockout analyses (CRISPR/Cas9) identified that ALVAC stimulated the cGAS/IFI16-STING-Type I IFN pathway to prime AIM2, which was functionally required for ALVAC-induced inflammasome activation. We also provided evidence that different from ALVAC, Ad5 vector itself was unable to induce inflammasome activation, which was related to its inability to stimulate STING-Type I IFN pathway and to provide inflammasome priming signals. In pre-conditioned APCs, Ad5 vector could stimulate inflammasome activation through AIM2-independent mechanism. Therefore, our study identifies AIM2 inflammasome and cGAS/IFI16-STING-Type I IFN pathway as novel mechanism for host innate immunity to ALVAC vaccine vector.

show abstract

“…It is noteworthy that the inflammasome is not only an innate responder to pathogenic and danger signals, but can also affect adaptive autoimmunity. [101][102][103] Growing evidence highlights the role of inflammasome-dependent cytokines in shaping the adaptive immune response, as exemplified by the capacity of IL-1b to support T-helper 17 responses or by the finding that IL-18 evokes antigen-independent interferon-c secretion by memory CD8 þ T cells. 102 I.V.…”

Section: Complex Regional Pain Syndromementioning

confidence: 99%

The inflammasome as a target for pain therapy

Zhang¹,

Li²,

Li³

et al. 2016

British Journal of Anaesthesia

View full text Add to dashboard Cite

The interleukin-1 family of cytokines are potent inducers of inflammation and pain. Proteolytic activation of this family of cytokines is under the control of several innate immune receptors that coordinate to form large multiprotein signalling platforms, termed inflammasomes. Recent evidence suggests that a wide range of inflammatory diseases, cancers, and metabolic and autoimmune disorders, in which pain is a common complaint, may be coordinated by inflammasomes. Activation of inflammasomes results in cleavage of caspase-1, which subsequently induces downstream initiation of several potent pro-inflammatory cascades. Therefore, it has been proposed that targeting inflammasome activity may be a novel and effective therapeutic strategy for these pain-related diseases. The purpose of this narrative review article is to provide the reader with an overview of the activation and regulation of inflammasomes and to investigate the potential therapeutic role of inflammasome inhibition in the treatment of diseases characterized by pain, including the following: complex regional pain syndrome, gout, rheumatoid arthritis, inflammatory pain, neuropathic pain, chronic prostatitis, chronic pelvic pain syndrome, and fibromyalgia. We conclude that the role of the inflammasome in pain-associated diseases is likely to be inflammasome subtype and disease specific. The currently available evidence suggests that disease-specific targeting of the assembly and activity of the inflammasome complex may be a novel therapeutic opportunity for the treatment of refractory pain in many settings.

show abstract

Innate and adaptive effects of inflammasomes on T cell responses

Cited by 38 publications

References 56 publications

Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes

Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes

Priming and Activation of Inflammasome by Canarypox Virus Vector ALVAC via the cGAS/IFI16–STING–Type I IFN Pathway and AIM2 Sensor

The inflammasome as a target for pain therapy

Contact Info

Product

Resources

About