Cell-specific conditional deletion of interleukin-1 (IL-1) ligands and its receptors: a new toolbox to study the role of IL-1 in health and disease

Pinteaux, Emmanuel; Abdulaal, Wesam H.; Mufazalov, Ilgiz A.; Humphreys, Neil; Simonsen-Jackson, Maj; Francis, Sheila; Müller, Werner; Waisman, Ari

doi:10.1007/s00109-020-01928-5

Cited by 7 publications

(3 citation statements)

References 64 publications

(78 reference statements)

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“…From these combined reports, we can at least conclude three important findings considering IL-1R signaling in the regulation of CD8 + T cell immunity: (1) both IL-1R1 expression on CD8 + T cells as well as peripheral expression of the receptor complex contribute to IL-1-mediated CD8 + T cell activation; (2) different bodies of evidence indicate a segregation in this contribution, meaning that the different cellular targets of IL-1 possibly regulate different aspects of the CD8 + T cell response; (3) the relative importance of IL-1R signaling in different cell populations could be context-dependent and thus variable in naive mice versus virus-infected or tumor-bearing backgrounds. The recent generation of Il1r1 -floxed mice is therefore very exciting, as this will allow for detailed dissection of the importance of IL-1R signaling in different cell populations under specific conditions ( 251 ).…”

Section: How Il-1 Affects the Main Players Of The Immune Response To mentioning

confidence: 99%

Interleukin-1 as Innate Mediator of T Cell Immunity

2021

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The three-signal paradigm tries to capture how the innate immune system instructs adaptive immune responses in three well-defined actions: (1) presentation of antigenic peptides in the context of MHC molecules, which allows for a specific T cell response; (2) T cell co-stimulation, which breaks T cell tolerance; and (3) secretion of polarizing cytokines in the priming environment, thereby specializing T cell immunity. The three-signal model provides an empirical framework for innate instruction of adaptive immunity, but mainly discusses STAT-dependent cytokines in T cell activation and differentiation, while the multi-faceted roles of type I IFNs and IL-1 cytokine superfamily members are often neglected. IL-1α and IL-1β are pro-inflammatory cytokines, produced following damage to the host (release of DAMPs) or upon innate recognition of PAMPs. IL-1 activity on both DCs and T cells can further shape the adaptive immune response with variable outcomes. IL-1 signaling in DCs promotes their ability to induce T cell activation, but also direct action of IL-1 on both CD4+ and CD8+ T cells, either alone or in synergy with prototypical polarizing cytokines, influences T cell differentiation under different conditions. The activities of IL-1 form a direct bridge between innate and adaptive immunity and could therefore be clinically translatable in the context of prophylactic and therapeutic strategies to empower the formation of T cell immunity. Understanding the modalities of IL-1 activity during T cell activation thus could hold major implications for rational development of the next generation of vaccine adjuvants.

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Section: How Il-1 Affects the Main Players Of The Immune Response To mentioning

confidence: 99%

Interleukin-1 as Innate Mediator of T Cell Immunity

2021

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“…Interleukin type 1-beta (IL-β) is a pivotal cytokine in several second messenger signaling pathways in both physiological and pathological processes [ 32 ]. IL-1β acts as a modulator during ovulation, in oocyte maturation, during early embryonic development [ 33 , 34 ], and in the activation of the inflammatory response [ 28 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Equine Placentitis in Mares Induces the Secretion of Pro-Inflammatory Cytokine eIL-1β and the Active Extracellular Matrix Metalloproteinase (MMP)-9

Morales-Vázquez,

Meza-Serrano,

Lara-Pereyra

et al. 2023

Veterinary Sciences

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Equine placentitis is characterized by infection and inflammation of the placenta. Different biomarkers associated with this inflammatory response have been evaluated in experimentally induced equine placentitis, but not in pregnant mares with spontaneous placentitis. The aim of the current study was to determine the concentration of eIL-1β and the activity of proMMP-2 and proMMP-9 in the serum of healthy mares and mares with placentitis on days 240 and 320 of gestation to explore whether these biomarkers are associated with equine maternal placentitis and/or with the birth of an infected or inviable foals. Serum samples were collected from sixteen pregnant English Thoroughbred mares, retrospectively classified as follows: (1) healthy mares with full-term gestation; and (2) mares with ultrasonographic signs of placentitis. The health of each foal was examined at birth, and it was decided to classify the cases into four groups: (1) healthy mares delivering a healthy foals (HM-HF, n = 6); (2) mares with USP delivering a healthy foal (USP-HF, n = 3); (3) mares with USP delivering a live septic foal (USP-LSeF, n = 4); and (4) mares with USP delivering a dead foal (USP-DF, n = 3). eIL-1β was quantified by ELISA, and proMMP-2 and proMMP-9 activity by gelatin zymography electrophoresis. In healthy mares, the serum concentrations of eIL-1β underwent a significant 16.5-fold increase from day 240 to day 320 of gestation. Although similar results were found in the mares with ultrasonographic signs of placentitis that delivered a healthy foal, those delivering a live septic or nonviable foal exhibited much higher concentrations of eIL-1β. proMMP-2 and proMMP-9 activity was not associated with maternal placentitis, foal infection, or death. Hence, the presence of placentitis severe enough to affect the health of the foal can be confirmed or discarded by determining the eIL-1β concentration in mares that have shown ultrasonographic signs of placentitis.

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“…Pseudomonas aeruginosa quorum sensing related molecules affect the airway epithelial immune response IL-1β 281,282 . Just like IL-33, IL-1α functions as an alarmin and is released upon cell death.…”

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confidence: 99%

Alternatives to antibiotics

Beenker¹

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Antibiotic resistance is a growing problem, leading to ineffective antibiotic treatments, causing bacterial infections to be lethal again. Therefore, new alternatives are needed to fight bacterial infections. Targeting bacterial quorum sensing, might be a promising approach. Quorum sensing (QS) is a bacterial communication system via which bacteria regulate their gene expression based on cell density. In other words, when there are a lot of bacteria, different genes are activated that are beneficial for collaboration. These genes include genes involved in virulence factor production (which cause tissue damage) and biofilm formation (which makes the bacteria less susceptible for antibiotics). Therefore, inhibition of QS might have beneficial effects, including less tissue damage and higher susceptibility to antibiotics. QS inhibitors have also shown positive outcomes in animal models. However, the role of QS during human infections is still underexplored. In this thesis, we focused on the potential of QS inhibition as alternative treatment against bacterial infection. We searched for novel QS inhibitors using a library of more than 10,000 fungal filtrates. This showed that natural compounds produced by fungi still hold great promise to find novel QS inhibitors since various active compounds were identified. Paecilomycone showed the greatest potential by limiting production of virulence factors and biofilm formation in P. aeruginosa, a bacteria that is notorious for causing infections in immunocompromised patients, including individuals with CF. In addition, we set up a new platform to study the role of QS during infection using co-cultures of P. aeruginosa bacteria with airway organoids. This research showed that organoids can indeed be used to study the interplay between epithelium and bacteria. The epithelium showed a strong immune response after infection with P. aeruginosa, while P. aeruginosa bacteria upregulated genes involved in infection. However, genes involved with QS were inhibited. This suggests that the role of QS during human infection might be limited. Therefore, we need to focus on learning more about the role of QS during human infection before developing QS into the clinic.

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Cell-specific conditional deletion of interleukin-1 (IL-1) ligands and its receptors: a new toolbox to study the role of IL-1 in health and disease

Cited by 7 publications

References 64 publications

Interleukin-1 as Innate Mediator of T Cell Immunity

Interleukin-1 as Innate Mediator of T Cell Immunity

Equine Placentitis in Mares Induces the Secretion of Pro-Inflammatory Cytokine eIL-1β and the Active Extracellular Matrix Metalloproteinase (MMP)-9

Alternatives to antibiotics

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