Treponemapallidum Dysregulates Monocytes and Promotes the Expression of IL-1β and Migration in Monocytes Through the mTOR Signaling Pathway

Liu, Wen-Na; Jiang, Xiaoyong; Xu, Yan-Zhu; Sun, Xuxu; Wu, Kaixuan; Hu, Xinlin; Lin, Yong; Lin, Li‐Rong; Tong, Man‐Li; Liu, Li‐Li

doi:10.3389/fcimb.2020.592864

Cited by 11 publications

(5 citation statements)

References 38 publications

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“…Consistent with our findings, studies by Liu et al. have demonstrated that TP can augment the expression of CD14 and CD16 in monocytes in vitro , leading to the differentiation of monocytes into intermediate monocytes ( 30 ). This increase in intermediate monocytes may exert a profound impact on T cell subset differentiation and contribute to immune evasion.…”

Section: Discussionsupporting

confidence: 93%

“…Intermediate monocytes are actively involved in antigen presentation and inflammation, whereas classical monocytes primarily function as immune surveillance cells, specializing in immune phagocytosis (29). Consistent with our findings, studies by Liu et al have demonstrated that TP can augment the expression of CD14 and CD16 in monocytes in vitro, leading to the differentiation of monocytes into intermediate monocytes (30). This increase in intermediate monocytes may exert a profound impact on T cell subset differentiation and contribute to immune evasion.…”

Section: Figuresupporting

confidence: 90%

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Immunophenotypic variations in syphilis: insights from Mendelian randomization analysis

Xie,

Tang,

Shen

et al. 2024

Front. Immunol.

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BackgroundInfection with Treponema pallidum instigates complex immune responses. Prior research has suggested that persistent Treponema pallidum infection can manipulate host immune responses and circumvent host defenses. However, the precise role of immune cells in Treponema pallidum infection across different stages remains a contentious issue.MethodsUtilizing summary data from genome-wide association studies, we employed a two-sample Mendelian randomization method to investigate the association between 731 immunophenotypes and syphilis. Syphilis was categorized into early and late stages in this study to establish a more robust correlation and minimize bias in database sources.ResultsOur findings revealed that 33, 36, and 27 immunophenotypes of peripheral blood were associated with syphilis (regardless of disease stage), early syphilis and late syphilis, respectively. Subsequent analysis demonstrated significant variations between early and late syphilis in terms of immunophenotypes. Specifically, early syphilis showcased activated, secreting, and resting regulatory T cells, whereas late syphilis was characterized by resting Treg cells. More B cells subtypes emerged in late syphilis. Monocytes in early syphilis exhibited an intermediate and non-classical phenotype, transitioning to classical in late syphilis. Early syphilis featured naive T cells, effector memory T cells, and terminally differentiated T cells, while late syphilis predominantly presented terminally differentiated T cells. Immature myeloid-derived suppressor cells were evident in early syphilis, whereas the dendritic cell immunophenotype was exclusive to late syphilis.ConclusionMultiple immunophenotypes demonstrated associations with syphilis, showcasing substantial disparities between the early and late stages of the disease. These findings hold promise for informing immunologically oriented treatment strategies, paving the way for more effective and efficient syphilis interventions.

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Section: Discussionsupporting

confidence: 93%

Section: Figuresupporting

confidence: 90%

Immunophenotypic variations in syphilis: insights from Mendelian randomization analysis

Xie,

Tang,

Shen

et al. 2024

Front. Immunol.

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“…We believe these two concurrent events led to an enhanced interaction between IFN-γ, TNF-α and monocytes, resulting in an improved phagocytic ability of monocytes during sepsis ( 32 ), and the production of IL-1β. The production of these pro-inflammatory cytokines can promote the antigen presentation function of monocytes, a key mechanism in the resolution of an infection ( 23 , 33 ). However, our gene expression results suggest that the antigen presentation ability of monocytes is decreased during acute sepsis.…”

Section: Discussionmentioning

confidence: 99%

Dynamic immune status analysis of peripheral blood mononuclear cells in patients with Klebsiella pneumoniae bloodstream infection sepsis using single-cell RNA sequencing

Zhang,

Han

et al. 2024

Front. Immunol.

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BackgroundKlebsiella pneumoniae is a common Gram-negative bacterium. Blood infection caused by K. pneumoniae is one of the most common causes of human sepsis, which seriously threatens the life of patients. The immune status of peripheral blood mononuclear cells (PBMCs) based on single-cell RNA sequencing (scRNA-seq) in acute stage and recovery stage of sepsis caused by K. pneumoniae bloodstream infection has not been studied.MethodsA total of 13 subjects were included in this study, 3 healthy controls, 7 patients with K. pneumoniae bloodstream infection in the acute stage (4 patients died), and 3 patients in the recovery stage. Peripheral blood of all patients was collected and PBMCs were isolated for scRNA-seq analysis. We studied the changes of PBMCs components, signaling pathways, differential genes, and cytokines in acute and recovery stages.ResultsDuring K. pneumoniae acute infection we observed a decrease in the proportion of T cells, most probably due to apoptosis and the function of T cell subtypes was disorder. The proportion of monocytes increased in acute stage. Although genes related to their phagocytosis function were upregulated, their antigen presentation capacity-associated genes were downregulated. The expression of IL-1β, IL-18, IFNGR1 and IFNGR2 genes was also increased in monocytes. The proportion of DCs was depleted during the acute stage and did not recover during sepsis recovery. DCs antigen presentation was weakened during the acute stage but recovered fast during the recovery stage. pDCs response to MCP-1 chemokine was weakened, they recovered it quickly during the recovery stage. B cells showed apoptosis both in the acute stage and recovery stage. Their response to complement was weakened, but their antigen presentation function was enhanced. The proportion of NK cells stable during all disease’s stages, and the expression of IFN-γ gene was upregulated.ConclusionThe proportion of PBMCs and their immune functions undergo variations throughout the course of the disease, spanning from the acute stage to recovery. These findings provide new insights into the mechanism of PBMCs immune function during K. pneumoniae bloodstream infection sepsis and recovery and sets the basis for further understanding and treatment.

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“…57 T. pallidum, Tp92, Tp47, FlaA2, Tp0751, TpF1 (tp1038) and Tp0768 stimulate neutrophils, dendritic cells (DCs), THP-1 cells and macrophages to secrete a series of cytokines, including IL-8, IL-12, IL-1β, TNF-α, IL-6 and IL-12. [98][99][100][101][102][103][104][105][106][107][108][109] On the other hand, YTHDF1 expression is increased in cells following Tp-induced activation of macrophages. When YTHDF1 recognizes the m6A methylation site on SOCS3 mRNA, it binds to it and stimulates translation, which in turn decreases the release of inflammatory molecules including TNF-and IL-1, hence playing an anti-inflammatory role.…”

Section: T Pallidum-mediated Inflammatory Response Via Cytokinesmentioning

confidence: 99%

“…Meanwhile, T. pallidum infection stimulates a strong innate immune response, accompanied by inflammation and injury of ECs 57 . T. pallidum , Tp92, Tp47, FlaA2, Tp0751, TpF1 ( tp1038 ) and Tp0768 stimulate neutrophils, dendritic cells (DCs), THP‐1 cells and macrophages to secrete a series of cytokines, including IL‐8, IL‐12, IL‐1β, TNF‐α, IL‐6 and IL‐12 98–109 . On the other hand, YTHDF1 expression is increased in cells following Tp‐induced activation of macrophages.…”

Section: T Pallidum‐mediated Ecdmentioning

confidence: 99%

Endothelial dysfunction of syphilis: Pathogenesis

Liu,

Zhang,

Xiong

et al. 2024

Acad Dermatol Venereol

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Treponema pallidum is the causative factor of syphilis, a sexually transmitted disease (STD) characterized by perivascular infiltration of inflammatory cells, vascular leakage, swelling and proliferation of endothelial cells (ECs). The endothelium lining blood and lymphatic vessels is a key barrier separating body fluids from host tissues and is a major target of T. pallidum. In this review, we focus on how T. pallidum establish intimate interactions with ECs, triggering endothelial dysfunction such as endothelial inflammation, abnormal repairment and damage of ECs. In addition, we summarize that migration and invasion of T. pallidum across vascular ECs may occur through two pathways. These two mechanisms of transendothelial migration are paracellular and cholesterol‐dependent, respectively. Herein, clarifying the relationship between T. pallidum and endothelial dysfunction is of great significance to provide novel strategies for diagnosis and prevention of syphilis, and has a great potential prospect of clinical application.

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Treponemapallidum Dysregulates Monocytes and Promotes the Expression of IL-1β and Migration in Monocytes Through the mTOR Signaling Pathway

Cited by 11 publications

References 38 publications

Immunophenotypic variations in syphilis: insights from Mendelian randomization analysis

Immunophenotypic variations in syphilis: insights from Mendelian randomization analysis

Dynamic immune status analysis of peripheral blood mononuclear cells in patients with Klebsiella pneumoniae bloodstream infection sepsis using single-cell RNA sequencing

Endothelial dysfunction of syphilis: Pathogenesis

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