Bacterial infection reinforces host metabolic flux from arginine to spermine for NLRP3 inflammasome evasion

Jiang, Jiatiao; Wang, Wenwen; Sun, Fei; Zhang, Yuanxing; Liu, Qin; Yang, Dahai

doi:10.1016/j.celrep.2021.108832

Cited by 21 publications

(15 citation statements)

References 62 publications

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“…LncRNA Neat1 is associated with NLRP3 , NLRC4 , and AIM2 inflammasomes in mouse macrophages to increase their assembly and subsequent pro-caspase-1 processing ( Zhang et al, 2019 ). ROS-induced lysosome malfunction is a vital inducement of pyroptosis, and the arginine metabolism pathway participates in NLRP3 inflammasome inhibition ( Jiang et al, 2021 ; Li et al, 2021 ). Glycolytic metabolism can impose stress on DNA replication and activate AIM2 inflammasome ( Fidler et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Pyroptosis-Related Long Non-coding RNA Signature for Hepatocellular Carcinoma

Yang

Liu

2021

Front. Cell Dev. Biol.

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Background: Hepatocellular carcinoma (HCC) is a highly aggressive malignant disease, and numerous studies have demonstrated that an inflammatory environment can induce normal cells to transform into cancerous.Methods: We integrated genomic data to comprehensively assess the association between pyroptosis and tumor microenvironment (TME) cell-infiltrating characteristics in HCC, as well as the potential molecular function and clinical significance of lncRNA.Results: The analysis of CNV alteration frequency displayed that CNV changes were common in 33 PRGs, and most were focused on copy number amplification. As a result of lasso regression analysis, nine differentially expressed lncRNAs (AL031985.3, NRAV, OSMR-AS1, AC073611.1, MKLN1-AS, AL137186.2, AL049840.4, MIR4435-2HG, and AL118511.1) were selected as independent prognosis factors of HCC patients. Patients at high risk have poorer survival than those in the low-risk group in training and testing cohorts. A low-risk score was significantly associated with an IC50 of chemotherapeutics such as bortezomib (p < 0.001), but a high-risk score was significantly linked to docetaxel (p < 0.001), implying that signature served as a prospective predictor for chemosensitivity.Conclusion: This work suggests pyroptosis-related lncRNAs features and their potential mechanisms on tumor microenvironment. The exploration may assist in identifying novel biomarkers and assist patients in predicting their prognosis, clinical diagnosis, and management.

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Section: Discussionmentioning

confidence: 99%

Development and Validation of a Pyroptosis-Related Long Non-coding RNA Signature for Hepatocellular Carcinoma

Yang

Liu

2021

Front. Cell Dev. Biol.

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“…Nitrate reduction to di-nitrogen by Brucella abortus has been demonstrated to result in the presence of intermediate NO in iNOS-deficient cells and thus inhibition of the NLRP3 inflammasome ( 165 ) ( Figure 2B ). Furthermore, upon macrophage engulfment, the fish pathogen Edwardsiella piscicida delivers spermine to the cytosol in a T3SS-dependent manner, mediated by recruitment of arginine importer cationic acid transporter 1 (mCAT-1) and putrescin exporter organic cation transporter 2 (Oct-2) to the bacteria-containing vacuole ( 166 ). Cytosolic accumulation of spermine then inhibits the K + efflux-dependent activation of the NLRP3 inflammasome ( 166 , 167 ) ( Figure 2B ).…”

Section: Inflammasome Forming Nlrsmentioning

confidence: 99%

“…Furthermore, upon macrophage engulfment, the fish pathogen Edwardsiella piscicida delivers spermine to the cytosol in a T3SS-dependent manner, mediated by recruitment of arginine importer cationic acid transporter 1 (mCAT-1) and putrescin exporter organic cation transporter 2 (Oct-2) to the bacteria-containing vacuole ( 166 ). Cytosolic accumulation of spermine then inhibits the K + efflux-dependent activation of the NLRP3 inflammasome ( 166 , 167 ) ( Figure 2B ). These studies demonstrate how the interplay between bacterial and host metabolism can regulate innate immune responses.…”

Section: Inflammasome Forming Nlrsmentioning

confidence: 99%

Bacterial subversion of NLR-mediated immune responses

et al. 2022

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Members of the mammalian Nod-like receptor (NLR) protein family are important intracellular sensors for bacteria. Bacteria have evolved under the pressure of detection by host immune sensing systems, leading to adaptive subversion strategies to dampen immune responses for their benefits. These include modification of microbe-associated molecular patterns (MAMPs), interception of innate immune pathways by secreted effector proteins and sophisticated instruction of anti-inflammatory adaptive immune responses. Here, we summarise our current understanding of subversion strategies used by bacterial pathogens to manipulate NLR-mediated responses, focusing on the well-studied members NOD1/2, and the inflammasome forming NLRs NLRC4, and NLRP3. We discuss how bacterial pathogens and their products activate these NLRs to promote inflammation and disease and the range of mechanisms used by bacterial pathogens to evade detection by NLRs and to block or dampen NLR activation to ultimately interfere with the generation of host immunity. Moreover, we discuss how bacteria utilise NLRs to facilitate immunotolerance and persistence in the host and outline how various mechanisms used to attenuate innate immune responses towards bacterial pathogens can also aid the host by reducing immunopathologies. Finally, we describe the therapeutic potential of harnessing immune subversion strategies used by bacteria to treat chronic inflammatory conditions.

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“…Importantly the addition of the ve investigational biomarkers SP-A, KL-6, LDH, CRP, and tIgE signi cantly increased the AUC to 0.756 for comparison of Stability AUC -Exacerbation AUC in IPAF cohort (P < 0.05 for the difference between the curves) (Table3, Figure 4). [27,[39][40][41][42][43][44][45][46][47][48][49] Pulmonary function testing (PFT) and Blood cell test Whether IPAF is compared with IPF, or simply a comparison among the three strati cations of the severity of IPAF (p<0.05), apart from DLCO, which identi ed 36 patients with moderate interstitial lung disease, the remaining PFT items, including FVC, FEV1 showed that the patients in two cohorts did not show signi cant clinical signi cance in PFT (Figure 5). No abnormality was found in the selected cytokines in the blood cell test in the IPAF and IPF cohorts.…”

Section: Combinatorial Signaturementioning

confidence: 99%

Detection of interstitial pneumonia with autoimmune features and idiopathic pulmonary fibrosis are enhanced by involvement of matrix metalloproteinases levels and clinical diagnosis

Liu

Xue

Zhang

et al. 2022

Clinical Laboratory Analysis

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Background: Higher detection of interstitial pneumonia with autoimmune features (IPAF), idiopathic pulmonary brosis (IPF) has signi cant diagnostic and therapeutic implications. Some MMPs have been reliable diagnostic biomarkers in IPAF and IPF in previous studies, yet relevant reliability remains to be recognized. Material and Methods: 36 ILD patients, including 31 IPAF patients (Mean ± SD, 50.20 ± 5.10 years; 16 (51.6%) females) and 5 IPF patients (Mean ± SD, 61.20 ± 6.73 years; 1 (20.0%) females) were retrospectively enrolled. Serial serum samples were collected from corresponding patients between January 2019 and December 2020. Notably, Serum MMPs levels were measured by U-PLEX Biomarker Group 1(Human) Multiplex Assays (MSD, USA).Results: A combination of MMPs, combinatorial biomarkers and was strongly associated with the above clinical subjects (AUC, 0.597 for Stability vs. Improvement and 0.756 for Stability vs. Exacerbation).Importantly, the AUC of MMP-12 reaches 0.730 (P<0.05, Stability AUC vs. Improvement AUC) while MMP-13 reaches 0.741 (P<0.05, Stability AUC vs. Exacerbation AUC) showed better academic performance than other MMPs in two comparisons.Conclusions: Clinical risk factors and MMPs are strongly associated with either strati cation of the degree of disease of progression of IPAF or in two IPAF and IPF independent cohorts. To our knowledge, this is the rst to illustrate that MMP-12 and MMP-13 may be expected to become typical promising biomarkers in Improvement -IPAF and Exacerbation -IPAF, respectively.

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Bacterial infection reinforces host metabolic flux from arginine to spermine for NLRP3 inflammasome evasion

Cited by 21 publications

References 62 publications

Development and Validation of a Pyroptosis-Related Long Non-coding RNA Signature for Hepatocellular Carcinoma

Development and Validation of a Pyroptosis-Related Long Non-coding RNA Signature for Hepatocellular Carcinoma

Bacterial subversion of NLR-mediated immune responses

Detection of interstitial pneumonia with autoimmune features and idiopathic pulmonary fibrosis are enhanced by involvement of matrix metalloproteinases levels and clinical diagnosis

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