scholarly journals Glucose Triggers ATP Secretion from Bacteria in a Growth-Phase-Dependent Manner

2013 ◽  
Vol 79 (7) ◽  
pp. 2328-2335 ◽  
Author(s):  
Ippei Hironaka ◽  
Tadayuki Iwase ◽  
Shinya Sugimoto ◽  
Ken-ichi Okuda ◽  
Akiko Tajima ◽  
...  
Keyword(s):  
Stationary Phase ◽  
Growth Phase ◽  
Cell Function ◽  
Immune Cell ◽  
Dependent Manner ◽  
T Helper 17 ◽  
Content Type ◽  
Cell Functions ◽  
Atp Secretion ◽  
Enterococcus Gallinarum

ABSTRACTATP modulates immune cell functions, and ATP derived from gut commensal bacteria promotes the differentiation of T helper 17 (Th17) cells in the intestinal lamina propria. We recently reported thatEnterococcus gallinarum, isolated from mice and humans, secretes ATP. We have since found and characterized several ATP-secreting bacteria. Of the tested enterococci,Enterococcus mundtiisecreted the greatest amount of ATP (>2 μM/108cells) after overnight culture. Glucose, not amino acids and vitamins, was essential for ATP secretion fromE. mundtii. Analyses of energy-deprived cells demonstrated that glycolysis is the most important pathway for bacterial ATP secretion. Furthermore, exponential-phaseE. mundtiiandEnterococcus faecaliscells secrete ATP more efficiently than stationary-phase cells. Other bacteria, includingPseudomonas aeruginosa,Escherichia coli, andStaphylococcus aureus, also secrete ATP in exponential but not stationary phase. These results suggest that various gut bacteria, including commensals and pathogens, might secrete ATP at any growth phase and modulate immune cell function.

scholarly journals Function of the Pyruvate Oxidase-Lactate Oxidase Cascade in Interspecies Competition between Streptococcus oligofermentans and Streptococcus mutans

2012 ◽  
Vol 78 (7) ◽  
pp. 2120-2127 ◽  
Author(s):  
Lei Liu ◽  
Huichun Tong ◽  
Xiuzhu Dong
Keyword(s):  
Stationary Phase ◽  
Streptococcus Mutans ◽  
Growth Phase ◽  
Large Degree ◽  
Interspecies Interactions ◽  
Lactate Oxidase ◽  
Interspecies Competition ◽  
Pyruvate Oxidase ◽  
Content Type

ABSTRACTComplex interspecies interactions occur constantly between oral commensals and the opportunistic pathogenStreptococcus mutansin dental plaque. Previously, we showed that oral commensalStreptococcus oligofermentanspossesses multiple enzymes for H2O2production, especially lactate oxidase (Lox), allowing it to out-competeS. mutans. In this study, through extensive biochemical and genetic studies, we identified a pyruvate oxidase (pox) gene inS. oligofermentans. Apoxdeletion mutant completely lost Pox activity, while ectopically expressedpoxrestored activity. Pox was determined to produce most of the H2O2in the earlier growth phase and log phase, while Lox mainly contributed to H2O2production in stationary phase. Bothpoxandloxwere expressed throughout the growth phase, while expression of theloxgene increased by about 2.5-fold when cells entered stationary phase. Since lactate accumulation occurred to a large degree in stationary phase, the differential Pox- and Lox-generated H2O2can be attributed to differential gene expression and substrate availability. Interestingly, inactivation ofpoxcauses a dramatic reduction in H2O2production from lactate, suggesting a synergistic action of the two oxidases in converting lactate into H2O2. In anin vitrotwo-species biofilm experiment, thepoxmutant ofS. oligofermentansfailed to inhibitS. mutanseven thoughloxwas active. In summary,S. oligofermentansdevelops a Pox-Lox synergy strategy to maximize its H2O2formation so as to win the interspecies competition.

scholarly journals Triptolide Modulates the Expression of Inflammation-Associated lncRNA-PACER and lincRNA-p21 in Mycobacterium tuberculosis–Infected Monocyte-Derived Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Ousman Tamgue ◽  
Julius Ebua Chia ◽  
Frank Brombacher
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Target Genes ◽  
Cell Function ◽  
Immune Cell ◽  
Biological Activities ◽  
Target Cells ◽  
Dependent Manner ◽  
Direct Targeting ◽  
Non Coding Rnas ◽  
Alamarblue Assay

Triptolide is a diterpene triepoxide, which performs its biological activities via mechanisms including induction of apoptosis, targeting of pro-inflammatory cytokines, and reshaping of the epigenetic landscape of target cells. However, the targeting of long non-coding RNAs (lncRNAs) by triptolide has not yet been investigated, despite their emerging roles as key epigenetic regulators of inflammation and immune cell function during Mycobacterium tuberculosis (Mtb) infection. Hence, we investigated whether triptolide targets inflammation-associated lncRNA-PACER and lincRNA-p21 and how this targeting associates with Mtb killing within monocyte-derived macrophages (MDMs).Using RT-qPCR, we found that triptolide induced the expression of lincRNA-p21 but inhibited the expression of lncRNA-PACER in resting MDMs in a dose- and time-dependent manner. Moreover, Mtb infection induced the expression of lincRNA-p21 and lncRNA-PACER, and exposure to triptolide before or after Mtb infection led to further increase of Mtb-induced expression of these lncRNAs in MDMs. We further found that contrary to lncRNA-PACER, triptolide time- and dose-dependently upregulated Ptgs-2, which is a proximal gene regulated by lncRNA-PACER. Also, low-concentration triptolide inhibited the expression of cytokine IL-6, a known target of lincRNA-p21. Mtb infection induced the expression of IL-6 and Ptgs-2, and triptolide treatment further increased IL-6 but decreased Ptgs-2 expression in Mtb-infected MDMs. The inverse relation between the expression of these lncRNAs and their target genes is concordant with the conception that these lncRNAs mediate, at least partially, the cytotoxic and/or anti-inflammatory activities of triptolide in both resting and activated MDMs. Using the CFU count method, we found that triptolide decreased the intracellular growth of Mtb HN878. The alamarBlue assay showed that this decreased Mtb HN878 growth was not as a result of direct targeting of Mtb HN878 by triptolide, but rather evoking MDMs’ intracellular killing mechanisms which we speculate could include triptolide-induced enhancement of MDMs’ effector killing functions mediated by lncRNA-PACER and lincRNA-p21. Altogether, these results provide proof of the modulation of lncRNA-PACER and lincRNA-p21 expression by triptolide, and a possible link between these lncRNAs, the enhancement of MDMs’ effector killing functions and the intracellular Mtb-killing activities of triptolide. These findings prompt for further investigation of the precise contribution of these lncRNAs to triptolide-induced activities in MDMs.

scholarly journals Decidual glycodelin-A polarizes human monocytes into a decidual macrophage-like phenotype through Siglec-7

2020 ◽  
Vol 133 (14) ◽  
pp. jcs244400 ◽  
Author(s):  
Madhavi Vijayan ◽  
Cheuk-Lun Lee ◽  
Vera H. H. Wong ◽  
Xia Wang ◽  
Kungfeng Bai ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Immune Cell ◽  
Fetal Loss ◽  
Cell Types ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Placental Development ◽  
Cell Functions ◽  
Surface Marker Expression ◽  
Glycodelin A

ABSTRACTDecidual macrophages constitute 20–30% of the total leukocytes in the uterus of pregnant women, regulating the maternal immune tolerance and placenta development. Abnormal number or activities of decidual macrophages (dMs) are associated with fetal loss and pregnancy complications, such as preeclampsia. Monocytes differentiate into dMs in a decidua-specific microenvironment. Despite their important roles in pregnancy, the exact factors that regulate the differentiation into dMs remain unclear. Glycodelin-A (PAEP, hereafter referred to as GdA) is a glycoprotein that is abundantly present in the decidua, and plays an important role in fetomaternal defense and placental development. It modulates the differentiation and activity of several immune cell types residing in the decidua. In this study, we demonstrated that GdA induces the differentiation of human monocytes into dM-like phenotypes in terms of transcriptome, cell surface marker expression, secretome, and regulation of trophoblast and endothelial cell functions. We found that Sialic acid-binding Ig-like lectin 7 (Siglec-7) mediates the binding and biological actions of GdA in a sialic acid-dependent manner. We, therefore, suggest that GdA, induces the polarization of monocytes into dMs to regulate fetomaternal tolerance and placental development.

scholarly journals The Nature of Antibacterial Adaptive Immune Responses against Staphylococcus aureus Is Dependent on the Growth Phase and Extracellular Peptidoglycan

2019 ◽  
Vol 88 (1) ◽  
Author(s):  
Payal P. Balraadjsing ◽  
Lisbeth D. Lund ◽  
Yuri Souwer ◽  
Sebastian A. J. Zaat ◽  
Hanne Frøkiær ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
T Cell ◽  
Stationary Phase ◽  
Growth Phase ◽  
Cell Response ◽  
Th17 Cell ◽  
Exponential Phase ◽  
Th1 Cell ◽  
Content Type

ABSTRACT Staphylococcus aureus has evolved different strategies to evade the immune response, which play an important role in its pathogenesis. The bacteria express and shed various cell wall components and toxins during different stages of growth that may affect the protective T cell responses to extracellular and intracellular S. aureus. However, if and how the dendritic cell (DC)-mediated T cell response against S. aureus changes during growth of the bacterium remain elusive. In this study, we show that exponential-phase (EP) S. aureus bacteria were endocytosed very efficiently by human DCs, and these DCs strongly promoted production of the T cell polarizing factor interleukin-12 (IL-12). In contrast, stationary-phase (SP) S. aureus bacteria were endocytosed less efficiently by DCs, and these DCs produced small amounts of IL-12. The high level of IL-12 production induced by EP S. aureus led to the development of a T helper 1 (Th1) cell response, which was inhibited after neutralization of IL-12. Furthermore, preincubation with the staphylococcal cell wall component peptidoglycan (PGN), characteristically shed during the exponential growth phase, modulated the DC response to EP S. aureus. PGN preincubation appeared to inhibit IL-12p35 expression, leading to downregulation of IL-12 and an increase of IL-23 production by DCs, enhancing Th17 cell development. Taken together, our data indicate that exponential-phase S. aureus bacteria induce a stronger IL-12-dependent Th1 cell response than stationary-phase S. aureus and that this Th1 cell response shifted toward a Th17 cell response in the presence of PGN.

scholarly journals Immune deconvolution and temporal mapping identifies stromal targets and developmental intervals for abrogating murine low-grade optic glioma formation

2021 ◽  
Author(s):  
Amanda de Andrade Costa ◽  
Jit Chatterjee ◽  
Olivia Cobb ◽  
Elizabeth Cordell ◽  
Astoria Chao ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Function ◽  
Immune Cell ◽  
Tumor Formation ◽  
Optic Glioma ◽  
Low Grade ◽  
Dependent Manner ◽  
Cancer Predisposition Syndrome

Abstract Background Brain tumor formation and progression are dictated by cooperative interactions between neoplastic and non-neoplastic cells. This stromal dependence is nicely illustrated by tumors arising in the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome, where children develop low-grade optic pathway gliomas (OPGs). Using several authenticated Nf1-OPG murine models, we previously demonstrated that murine Nf1-OPG growth is regulated by T cell function and microglia Ccl5 production, such that their inhibition reduces tumor proliferation in vivo. While these interactions are critical for established Nf1-OPG tumor growth, their importance in tumor formation has not been explored. Methods A combination of bulk and single cell RNA mouse optic nerve sequencing, immunohistochemistry, T cell assays, and pharmacologic and antibody-mediated inhibition methods were used in these experiments. Results We show that T cells and microglia are the main non-neoplastic immune cell populations in both murine and human LGGs. Moreover, we demonstrate that CD8 + T cells, the predominant LGG-infiltrating lymphocyte population, are selectively recruited through increased Ccl2 receptor (Ccr4) expression in CD8 +, but not CD4 +, T cells, in a NF1/RAS-dependent manner. Finally, we identify the times during gliomagenesis when microglia Ccl5 production (3-6 weeks of age) and Ccl2-mediated T cell infiltration (7-10 weeks of age) occur, such that temporally-restricted Ccl2 or Ccl5 inhibition abrogates tumor formation >3.5 months following the cessation of treatment. Conclusions Collectively, these findings provide proof-of-concept demonstrations that targeting stromal support during early gliomagenesis durably blocks murine LGG formation.

Phorbol ester-induced U-937 differentiation: effects on integrin α 5 gene transcription

2000 ◽  
Vol 278 (4) ◽  
pp. L703-L712 ◽  
Author(s):  
Bonnie K. Boles ◽  
Jeffrey Ritzenthaler ◽  
Thomas Birkenmeier ◽  
Jesse Roman
Keyword(s):  
Lung Injury ◽  
Cell Function ◽  
Immune Cell ◽  
Biological Effects ◽  
Surface Expression ◽  
Tumor Promoter ◽  
Dependent Manner ◽  
Activator Protein 1 ◽  
Monocytic Cell ◽  
Promoter Sequences

Lung injury is accompanied by increased deposition of fibronectin (FN) matrices. Activated monocytic cells recruited to sites of lung injury express integrin receptors for FN that mediate their interaction with this matrix. One such integrin, α5β1, mediates many of the biological effects of FN, and its expression may be important for immune cell function at sites of lung injury. Herein, we examine the expression of α5β1 in response to the tumor promoter phorbol 12-myristate 13-acetate (PMA) in the human promonocytic cell line U-937. We demonstrate that PMA enhanced the adherence of U-937 cells to FN by increasing the expression of both the α5- and β1-subunit mRNAs and the surface expression of the protein. In U-937 cells transfected with an α 5 promoter-reporter gene, we found that PMA induced the transcription of the α 5 gene by acting on very specific promoter sequences other than activator protein-1 in a protein kinase C-dependent manner. Lipopolysaccharide had a similar effect. Modulation of α5β1 expression may be important for regulation of monocytic cell function in lung inflammation after injury.

scholarly journals Tpl2 Promotes Innate Cell Recruitment and Effector T Cell Differentiation To Limit Citrobacter rodentium Burden and Dissemination

2017 ◽  
Vol 85 (10) ◽  
Author(s):  
Nicole V. Acuff ◽  
Xin Li ◽  
Krishna Latha ◽  
Tamas Nagy ◽  
Wendy T. Watford
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Function ◽  
Immune Cell ◽  
Cd4 T Cell ◽  
Citrobacter Rodentium ◽  
Wild Type ◽  
Content Type ◽  
Cell Recruitment ◽  
Ifn Γ

ABSTRACT Tumor progression locus 2 (Tpl2) is a serine-threonine kinase that regulates Th1 differentiation, secretion of the inflammatory cytokine gamma interferon (IFN-γ), and host defense against the intracellular pathogens Toxoplasma gondii, Listeria monocytogenes, and Mycobacterium tuberculosis. However, relatively little is known about the contribution of Tpl2 to Th17 differentiation and immune cell function during infection with an extracellular pathogen. The goal of this study was to determine whether Tpl2 influences the immune response generated to the extracellular bacterium Citrobacter rodentium, which induces a mixed Th1 and Th17 response. During peak infection with C. rodentium, Tpl2 −/− mice experienced greater bacterial burdens with evidence of dissemination to the liver and spleen but ultimately cleared the bacteria within 3 weeks postinfection, similar to the findings for wild-type mice. Tpl2 −/− mice also recruited fewer neutrophils and monocytes to the colon during peak infection, which correlated with increased bacterial burdens. In mixed bone marrow chimeras, Tpl2 was shown to play a T cell-intrinsic role in promoting both IFN-γ and interleukin-17A production during infection with C. rodentium. However, upon CD4 T cell transfer into Rag −/− mice, Tpl2 −/− CD4 T cells were as protective as wild-type CD4 T cells against the dissemination of bacteria and mortality. These data indicate that the enhanced bacterial burdens in Tpl2 −/− mice are not caused primarily by impairments in CD4 T cell function but result from defects in innate immune cell recruitment and function.

scholarly journals Metabolite releasing polymers control dendritic cell function by modulating their energy metabolism

2020 ◽  
Vol 8 (24) ◽  
pp. 5195-5203
Author(s):  
Joslyn L. Mangal ◽  
Sahil Inamdar ◽  
Yi Yang ◽  
Subhadeep Dutta ◽  
Mamta Wankhede ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Dendritic Cell ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Dendritic Cell Function ◽  
Cell Functions

Metabolites control immune cell functions, and delivery of these metabolites in a sustained manner modulate the function of the immune cells.

scholarly journals Plasma kallikrein modulates immune cell trafficking during neuroinflammation via PAR2 and bradykinin release

2018 ◽  
Vol 116 (1) ◽  
pp. 271-276 ◽  
Author(s):  
Kerstin Göbel ◽  
Chloi-Magdalini Asaridou ◽  
Monika Merker ◽  
Susann Eichler ◽  
Alexander M. Herrmann ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Cell Function ◽  
Immune Cell ◽  
Cellular Adhesion ◽  
Coagulation System ◽  
Intercellular Adhesion Molecule ◽  
Plasma Kallikrein ◽  
Dependent Manner ◽  
Cns Inflammation ◽  
Endothelial Cell Function

Blood–brain barrier (BBB) disruption and transendothelial trafficking of immune cells into the central nervous system (CNS) are pathophysiological hallmarks of neuroinflammatory disorders like multiple sclerosis (MS). Recent evidence suggests that the kallikrein-kinin and coagulation system might participate in this process. Here, we identify plasma kallikrein (KK) as a specific direct modulator of BBB integrity. Levels of plasma prekallikrein (PK), the precursor of KK, were markedly enhanced in active CNS lesions of MS patients. Deficiency or pharmacologic blockade of PK renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by a remarkable reduction of BBB disruption and CNS inflammation. In vitro analysis revealed that KK modulates endothelial cell function in a protease-activated receptor-2–dependent manner, leading to an up-regulation of the cellular adhesion molecules Intercellular Adhesion Molecule 1 and Vascular Cell Adhesion Molecule 1, thereby amplifying leukocyte trafficking. Our study demonstrates that PK is an important direct regulator of BBB integrity as a result of its protease function. Therefore, KK inhibition can decrease BBB damage and cell invasion during neuroinflammation and may offer a strategy for the treatment of MS.

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