Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis

Trivedi, Shubhanshi; Labuz, Daniel; Anderson, Cole; Araujo, Claudia V. de; Blair, Antoinette; Middleton, Elizabeth; Jensen, Ole T.; Tran, Alexander; Mulvey, Matthew A.; Campbell, Robert A.; Hale, J. Scott; Rondina, Matthew T.; Leung, Daniel T.

doi:10.7554/elife.55615

Cited by 24 publications

(44 citation statements)

References 41 publications

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“…Among the 6 members of the IL17 family, IL-17a is the symbol of the family and the most widely studied factor. 28 It can protect the host against extracellular pathogens, but it can also promote the inflammatory pathology of autoimmune diseases, similar to IL-17c. Previous experiments confirmed that the IL-17 family can activate anti-cytokines and chemokines in the MAPK, NF-κB and C/EBPS pathways.…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide Mononucleotide Alleviates Hyperosmolarity-Induced IL-17a Secretion and Macrophage Activation in Corneal Epithelial Cells/Macrophage Co-Culture System

Yu¹,

Pu²,

Dai³

et al. 2021

JIR

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Background Hyperosmosis stress (HS) was a key pathological factor in the development of dry eye disease (DED). Nicotinamide mononucleotide (NMN) demonstrated protective effects in the corneal damage, however, its role in the HS-induced DED remained unclear. Methods A NaCl based HS in-vitro model (500 mOsm) was generated and used in a co-culture system including corneal epithelial cells (CEC) and macrophage cell line RAW264.7. The effect of NMN on NAD+ metabolism and the expression of HS biomarker, tonicity-responsive element binding protein (TonEBP), was studied in the CEC. The cellular activity, including cell viability, apoptosis status and lactate dehydrogenase (LDH) release through trypan blue staining, flow cytometry and LDH assay, respectively. The mitochondrial membrane potential (MMP) assay would be conducted using the JC1 kit. The expression of IL-17a were detected using RT-PCR, ELISA and Western blot. After co-culture with the CEC in different group for 24 h, the phagocytosis ability and macrophage polarization were assessed in RAW264.7 cells co-cultured with CEC with or without HS or NMN treatment. Besides, the involvement of Notch pathway in the RAW264.7 would be analyzed. The potential involvement of Sirtuin 1 (SIRT1) and IL-17a in the crosstalk between CEC and macrophage was studied with SIRT1 inhibitor EX 527 and anti-IL-17a monoclonal antibody, respectively. Results NMN treatment increased NAD+ concentration and thus improved cell viability, reduced apoptotic rate and decreased the LDH release in HS-treated CEC. Besides, NMN alleviated HS-induced MMP, intracellular ROS and LDH release. Besides, it was confirmed NMN improve SIRT1 function and decreased the HS related IL-17a expression in CEC and then alleviated macrophage phagocytosis ability and M1 polarization based on a CEC-macrophage co-culture system. Moreover, NMN treatment of CEC in the CEC could moderate the subsequent macrophage activation through Notch pathway. SIRT1 activation and IL-17a inhibition was regarded as key progress in the function of NMN based on the application of EX 527 and anti-IL-17a antibody in the CEC-macrophage co-culture system. Conclusion The findings demonstrated that NMN could alleviated HS-induced DED status through regulating the CEC/macrophage interaction. Our data pointed to the role of SIRT1, IL-17a and Notch pathway in the function of NMN and then provided updated knowledge of potential NMN application in the management of DED.

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Section: Discussionmentioning

confidence: 99%

Nicotinamide Mononucleotide Alleviates Hyperosmolarity-Induced IL-17a Secretion and Macrophage Activation in Corneal Epithelial Cells/Macrophage Co-Culture System

Yu¹,

Pu²,

Dai³

et al. 2021

JIR

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“…In patients infected with bacteria and virus, the frequency of MAIT cells has been shown to be reduced in the blood (14,(19)(20)(21). In intestinal (22) and liver (23,24) studies, MAIT cells are activated to migrate to inflamed tissues and modulates immune responses in mucous tissues.…”

Section: Introductionmentioning

confidence: 99%

Mucosal Associated Invariant T Cells Were Activated and Polarized Toward Th17 in Chronic Obstructive Pulmonary Disease

Qiu

Kang

et al. 2021

Front. Immunol.

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Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by airway limitation accompanied with infiltration of inflammatory cells. Mucosal associated invariant T (MAIT) cells can recognize bacteria and play an important role in controlling host immune responses by producing cytokines. In this study, we characterized the function and the ability of MAIT cells to secrete cytokines measured by flow cytometry. In COPD patients, MAIT cells have the ability to produce more IL-17 and less IFN-γ compared to healthy individuals. We found that HLA-DR expression levels reflected the degree of inflammation and the proportion of IL-17 was significantly correlated with lung function in peripheral blood. In addition, we found that MAIT cells were highly expressed in the lung, and the increased expression of CXCR2, CXCL1 indicated that MAIT cells had the potential to migrate to inflammatory tissues. This evidence implies that MAIT cells may play a potential role in COPD immunopathology.

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“…Following i.p. injection, the bacteria enter the bloodstream and disseminate [56, 64, 65]. In our experiments, only 15% (2/13) of the mice infected with wild-type UTI89, and 0% (0/13) of the mice injected with UTI89Δ miaB, were viable after 48 hours (Fig.…”

Section: Resultsmentioning

confidence: 79%

Balanced Input from the tRNA Prenyltransferase MiaA Controls the Stress Resistance and Virulence Potential of Extraintestinal PathogenicEscherichia coli

Blango

Kincannon

et al. 2021

Preprint

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An ability to adapt to rapidly changing and often hostile environments is key to the success of many bacterial pathogens. In Escherichia coli, the highly conserved enzymes MiaA and MiaB mediate the sequential prenylation and methylthiolation of adenosine-37 within tRNAs that decode UNN codons. Here, we show that MiaA, but not MiaB, is critical to the fitness and virulence of extraintestinal pathogenic E. coli (ExPEC), a major cause of urinary tract and bloodstream infections. Deletion of miaA has pleiotropic effects, rendering ExPEC especially sensitive to stressors like nitrogen and oxygen radicals and osmotic shock. We find that stress can stimulate striking changes in miaA expression, which in turn can increase translational frameshifting and markedly alter the bacterial proteome. Cumulatively, these data indicate that ExPEC, and likely other organisms, can vary MiaA levels as a means to fine-tune translation and the spectrum of expressed proteins in response to changing environmental challenges.

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Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis

Cited by 24 publications

References 41 publications

Nicotinamide Mononucleotide Alleviates Hyperosmolarity-Induced IL-17a Secretion and Macrophage Activation in Corneal Epithelial Cells/Macrophage Co-Culture System

Nicotinamide Mononucleotide Alleviates Hyperosmolarity-Induced IL-17a Secretion and Macrophage Activation in Corneal Epithelial Cells/Macrophage Co-Culture System

Mucosal Associated Invariant T Cells Were Activated and Polarized Toward Th17 in Chronic Obstructive Pulmonary Disease

Balanced Input from the tRNA Prenyltransferase MiaA Controls the Stress Resistance and Virulence Potential of Extraintestinal PathogenicEscherichia coli

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