Tim-3 inhibits macrophage control of Listeria monocytogenes by inhibiting Nrf2

Wang, Zhiding; Sun, Dejun; Chen, Guojiang; Li, Ge; Dou, Shuaijie; Wang, Renxi; Xiao, He; Hou, Chunmei; Li, Yan; Feng, Jie; Shen, Beifen; Han, Gencheng

doi:10.1038/srep42095

Cited by 24 publications

(23 citation statements)

References 52 publications

(68 reference statements)

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“…Another potential therapeutic approach would be to modulate macrophage function to improve their antimicrobial potential against bacterial infections. The feasibility of such an approach has been suggested in a recent report of macrophage phagocytosis of L. monocytogenes ( 291 ). In this study, the engagement of receptor T cell immunoglobulin mucin-3 (Tim-3) on macrophages inhibited phagocytosis of L. monocytogenes by blocking nuclear erythroid 2-related factor 2 (Nrf2) signaling.…”

Section: Novel Therapeutic Opportunitiesmentioning

confidence: 99%

Control of Phagocytosis by Microbial Pathogens

2017

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Phagocytosis is a fundamental process of cells to capture and ingest foreign particles. Small unicellular organisms such as free-living amoeba use this process to acquire food. In pluricellular organisms, phagocytosis is a universal phenomenon that all cells are able to perform (including epithelial, endothelial, fibroblasts, etc.), but some specialized cells (such as neutrophils and macrophages) perform this very efficiently and were therefore named professional phagocytes by Rabinovitch. Cells use phagocytosis to capture and clear all particles larger than 0.5 µm, including pathogenic microorganisms and cellular debris. Phagocytosis involves a series of steps from recognition of the target particle, ingestion of it in a phagosome (phagocytic vacuole), maturation of this phagosome into a phagolysosome, to the final destruction of the ingested particle in the robust antimicrobial environment of the phagolysosome. For the most part, phagocytosis is an efficient process that eliminates invading pathogens and helps maintaining homeostasis. However, several pathogens have also evolved different strategies to prevent phagocytosis from proceeding in a normal way. These pathogens have a clear advantage to perpetuate the infection and continue their replication. Here, we present an overview of the phagocytic process with emphasis on the antimicrobial elements professional phagocytes use. We also summarize the current knowledge on the microbial strategies different pathogens use to prevent phagocytosis either at the level of ingestion, phagosome formation, and maturation, and even complete escape from phagosomes.

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Section: Novel Therapeutic Opportunitiesmentioning

confidence: 99%

Control of Phagocytosis by Microbial Pathogens

2017

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“…We previously reported that Tim‐3 plays a regulatory role in the innate immune response . To test whether L3G can inhibit Tim‐3 signalling in innate immune cells, the human monocyte‐macrophage cell line U937, which constitutively expresses Tim‐3, was cultured in the presence of different doses of L3G or isotype control.…”

Section: Resultsmentioning

confidence: 99%

“…We previously reported that Tim-3 plays a regulatory role in the innate immune response. 28,41 To test whether L3G can inhibit Tim-3 signalling in innate immune cells, the human monocyte-macrophage cell line U937, which constitutively expresses Tim-3, was cultured in the presence of different doses of L3G or isotype control. We found that the administration of L3G dose dependently increased IFN-γ and IL-8 production and IFN-α and IFN-β expression in U937 cells ( Figure 3A-D).…”

Section: Administration Of L3g Antibody Increases Cytokine Productimentioning

confidence: 99%

“…Recently, the significance of Tim‐3‐induced innate immune tolerance has attracted considerable attention in the field of immunotherapy. Our previous report revealed that Tim‐3 can induce infection and tumour tolerance by inhibiting macrophage activation . Therefore, the effects of Tim‐3 antibodies on innate immunity should also be investigated.…”

Section: Introductionmentioning

confidence: 99%

“…Our previous report revealed that Tim-3 can induce infection and tumour tolerance by inhibiting macrophage activation. [27][28][29] Therefore, the effects of Tim-3 antibodies on innate immunity should also be investigated.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Monoclonal antibody against human Tim‐3 enhances antiviral immune response

Hou

Dou

et al. 2019

Scand J Immunol

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T cell immunoglobulin and mucin domain protein 3 (Tim‐3) is an immune checkpoint inhibitor in T cells and innate immune cells. The deregulated upregulation of Tim‐3 is related to immune exhaustion in tumour and viral infection. To overcome Tim‐3‐mediated immune tolerance, we developed a novel monoclonal antibody against human Tim‐3 (L3G) and investigated its roles in inhibiting Tim‐3 signalling and overcoming immune tolerance in T cells and monocytes/macrophages. The administration of L3G to cultured peripheral blood mononuclear cells (PBMCs) significantly increased the production of IFN‐γ and IL‐2 and the expression of type I interferon. The administration of L3G also increased the production of IFN‐γ, IL‐8 and type I interferon in U937 cells and primary monocytes. We investigated the mechanisms by which L3G enhances pro‐inflammatory cytokine expression, and our data show that L3G enhances STAT1 phosphorylation in both monocytes/macrophages and T cells. Finally, in an H1N1 infection model of PBMCs and U937 cells, L3G decreased the viral load and enhanced the expression of interferon. Thus, we developed a functional antibody with therapeutic potential against Tim‐3‐mediated infection tolerance.

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The role of Nrf2 in autoimmunity and infectious disease: Therapeutic possibilities

Freeborn

Rockwell

2021

Advances in Immunopharmacology

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Tim-3 inhibits macrophage control of Listeria monocytogenes by inhibiting Nrf2

Cited by 24 publications

References 52 publications

Control of Phagocytosis by Microbial Pathogens

Control of Phagocytosis by Microbial Pathogens

Monoclonal antibody against human Tim‐3 enhances antiviral immune response

The role of Nrf2 in autoimmunity and infectious disease: Therapeutic possibilities

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