scholarly journals Staphylococcus aureus induces cell-surface expression of immune stimulatory NKG2D ligands on human monocytes

2020 ◽  
Vol 295 (33) ◽  
pp. 11803-11821 ◽  
Author(s):  
Maiken Mellergaard ◽  
Rikke Illum Høgh ◽  
Astrid Lund ◽  
Blanca Irene Aldana ◽  
Romain Guérillot ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune System ◽  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Glycolytic Flux ◽  
Mitochondrial Activity ◽  
Host Immune System ◽  
Human Monocytes ◽  
Nkg2d Ligands

Staphylococcus aureus is among the leading causes of bacterial infections worldwide. The pathogenicity and establishment of S. aureus infections are tightly linked to its ability to modulate host immunity. Persistent infections are often associated with mutant staphylococcal strains that have decreased susceptibility to antibiotics; however, little is known about how these mutations influence bacterial interaction with the host immune system. Here, we discovered that clinical S. aureus isolates activate human monocytes, leading to cell-surface expression of immune stimulatory natural killer group 2D (NKG2D) ligands on the monocytes. We found that expression of the NKG2D ligand ULBP2 (UL16-binding protein 2) is associated with bacterial degradability and phagolysosomal activity. Moreover, S. aureus–induced ULBP2 expression was linked to altered host cell metabolism, including increased cytoplasmic (iso)citrate levels, reduced glycolytic flux, and functional mitochondrial activity. Interestingly, we found that the ability of S. aureus to induce ULBP2 and proinflammatory cytokines in human monocytes depends on a functional ClpP protease in S. aureus. These findings indicate that S. aureus activates ULBP2 in human monocytes through immunometabolic mechanisms and reveal that clpP inactivation may function as a potential immune evasion mechanism. Our results provide critical insight into the interplay between the host immune system and S. aureus that has evolved under the dual selective pressure of host immune responses and antibiotic treatment. Our discovery of an immune stimulatory pathway consisting of human monocyte-based defense against S. aureus suggests that targeting the NKG2D pathway holds potential for managing persistent staphylococcal infections.

scholarly journals Cell Surface Expression and Function of the Macromolecular C1 Complex on the Surface of Human Monocytes

2012 ◽  
Vol 3 ◽  
Author(s):  
Kinga K. Hosszu ◽  
Alisa Valentino ◽  
Yan Ji ◽  
Mara Matkovic ◽  
Lina Pednekar ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Human Monocytes ◽  
And Function

Regulation of TCR-CD3 cell surface expression by Staphylococcus aureus enterotoxin superantigens

1995 ◽  
Vol 84 (1-2) ◽  
pp. 117-117
Author(s):  
Florence Niedergang ◽  
Agnès Hemar ◽  
Colin Hewitt ◽  
Michacl Owen ◽  
Alice Dautry-Varsat ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression

scholarly journals HIV-1 Vpr up-regulates expression of ligands for the activating NKG2D receptor and promotes NK cell–mediated killing

Blood ◽  
2010 ◽  
Vol 115 (7) ◽  
pp. 1354-1363 ◽  
Author(s):  
Jonathan Richard ◽  
Sardar Sindhu ◽  
Tram N. Q. Pham ◽  
Jean-Philippe Belzile ◽  
Éric A. Cohen
Keyword(s):  
Dna Damage ◽  
Cell Surface ◽  
Nk Cell ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Target Cells ◽  
Nkg2d Ligands ◽  
Infected Cells ◽  
Nkg2d Receptor ◽  
Hiv 1

AbstractHIV up-regulates cell-surface expression of specific ligands for the activating NKG2D receptor, including ULBP-1, -2, and -3, but not MICA or MICB, in infected cells both in vitro and in vivo. However, the viral factor(s) involved in NKG2D ligand expression still remains undefined. HIV-1 Vpr activates the DNA damage/stress-sensing ATR kinase and promotes G2 cell-cycle arrest, conditions known to up-regulate NKG2D ligands. We report here that HIV-1 selectively induces cell-surface expression of ULBP-2 in primary CD4+ T lymphocytes by a process that is Vpr dependent. Importantly, Vpr enhanced the susceptibility of HIV-1–infected cells to NK cell–mediated killing. Strikingly, Vpr alone was sufficient to up-regulate expression of all NKG2D ligands and thus promoted efficient NKG2D-dependent NK cell–mediated killing. Delivery of virion-associated Vpr via defective HIV-1 particles induced analogous biologic effects in noninfected target cells, suggesting that Vpr may act similarly beyond infected cells. All these activities relied on Vpr ability to activate the ATR-mediated DNA damage/stress checkpoint. Overall, these results indicate that Vpr is a key determinant responsible for HIV-1–induced up-regulation of NKG2D ligands and further suggest an immunomodulatory role for Vpr that may not only contribute to HIV-1–induced CD4+ T-lymphocyte depletion but may also take part in HIV-1–induced NK-cell dysfunction.

scholarly journals Phenotyping of Leukocytes and Leukocyte-Derived Extracellular Vesicles

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Lotte Hatting Pugholm ◽  
Rikke Bæk ◽  
Evo Kristina Lindersson Søndergaard ◽  
Anne Louise Schacht Revenfeld ◽  
Malene Møller Jørgensen ◽  
...  
Keyword(s):  
Immune System ◽  
Cell Surface ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Parent Cell ◽  
Phenotypic Differences ◽  
Immunological Markers ◽  
Cellular Expression

Extracellular vesicles (EVs) have a demonstrated involvement in modulating the immune system. It has been proposed that EVs could be used as biomarkers for detection of inflammatory and immunological disorders. Consequently, it is of great interest to investigate EVs in more detail with focus on immunological markers. In this study, five major leukocyte subpopulations and the corresponding leukocyte-derived EVs were phenotyped with focus on selected immunological lineage-specific markers and selected vesicle-related markers. The leukocyte-derived EVs displayed phenotypic differences in the 34 markers investigated. The majority of the lineage-specific markers used for identification of the parent cell types could not be detected on EVs released from monocultures of the associated cell types. In contrast, the vesicular presentation of CD9, CD63, and CD81 correlated to the cell surface expression of these markers, however, with few exceptions. Furthermore, the cellular expression of CD9, CD63, and CD81 varied between leukocytes present in whole blood and cultured leukocytes. In summary, these data demonstrate that the cellular and vesicular presentation of selected lineage-specific and vesicle-related markers may differ, supporting the accumulating observations that sorting of molecular cargo into EVs is tightly controlled.

scholarly journals Bordetella pertussis Infection of Primary Human Monocytes Alters HLA-DR Expression

2004 ◽  
Vol 72 (3) ◽  
pp. 1450-1462 ◽  
Author(s):  
Jennifer A. Shumilla ◽  
Vashti Lacaille ◽  
Tara M. C. Hornell ◽  
Jennifer Huang ◽  
Supraja Narasimhan ◽  
...  
Keyword(s):  
Cell Surface ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Surface Expression ◽  
Interleukin 10 ◽  
Cell Surface Expression ◽  
Human Monocytes ◽  
Pertussis Infection ◽  
Hla Dr ◽  
Ifn Γ

ABSTRACT Bordetella pertussis is the causative agent of whooping cough, a potentially lethal respiratory disease in children. In immunocompetent individuals, B. pertussis infection elicits an effective adaptive immune response driven by activated CD4+ T cells. However, live B. pertussis persists in the host for 3 to 4 weeks prior to clearance. Thus, B. pertussis appears to have evolved short-term mechanisms for immune system evasion. We investigated the effects of B. pertussis wild-type strain BP338 on antigen presentation in primary human monocytes. BP338 infection reduced cell surface expression of HLA-DR and CD86 but not that of major histocompatibility complex class I proteins. This change in cell surface HLA-DR expression reflected intracellular redistribution of HLA-DR. The proportion of peptide-loaded molecules was unchanged in infected cells, suggesting that intracellular retention occurred after peptide loading. Although B. pertussis infection of monocytes induced rapid and robust expression of interleukin-10 (IL-10), HLA-DR redistribution did not appear to be explained by increased IL-10 levels. BP338-infected monocytes exhibited reduced synthesis of HLA-DR dimers. Interestingly, those HLA-DR proteins that were generated appeared to be longer-lived than HLA-DR in uninfected monocytes. BP338 infection also prevented gamma interferon (IFN-γ) induction of HLA-DR protein synthesis. Using mutant strains of B. pertussis, we found that reduction in HLA-DR surface expression was due in part to the presence of pertussis toxin whereas the inhibition of IFN-γ induction of HLA-DR could not be linked to any of the virulence factors tested. These data demonstrate that B. pertussis utilizes several mechanisms to modulate HLA-DR expression.

scholarly journals TNF-αAutocrine Feedback Loops in Human Monocytes: The Pro- and Anti-Inflammatory Roles of the TNF-αReceptors Support the Concept of Selective TNFR1 BlockadeIn Vivo

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Jennie M. Gane ◽  
Robert A. Stockley ◽  
Elizabeth Sapey
Keyword(s):  
Cell Surface ◽  
Inflammatory Cytokine ◽  
Human Subjects ◽  
Expression Patterns ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Human Monocytes ◽  
Healthy Human ◽  
Anti Inflammatory

Selective TNFR1 blockade in inflammatory diseases is emerging as a clinical strategy. We studied the roles of the two TNF-αreceptors, TNFR1 and TNFR2, in human monocytes, the principal producer of TNF-αand central to many TNF-αdriven diseases. We hypothesised that TNF-αhas pro- and anti-inflammatory effects on monocytes, occurring differentially via TNFR1 and TNFR2. Monocytes were isolated from healthy human subjects and exposed to LPS, plus/minus the addition of blocking antibodies to TNF-αor its receptors. Pro- and anti-inflammatory cytokine production was quantified using real-time PCR and ELISAs. Cell surface expression of TNFR1/2 was measured by flow cytometry. We demonstrated that monocytes vary in the expression patterns of TNFR1 and TNFR2. Autocrine binding of TNF-αled to sustained upregulation of proinflammatory cytokines via TNFR1. In contrast, autocrine binding via TNFR2 upregulated theanti-inflammatory cytokine, IL-10, without proinflammatory effect. TNFR2 was responsible for binding soluble TNF-αsecreted by monocytes, clearing the cytokine from the pericellular environment. TNFR1 blockade did not change the cell surface expression of TNFR2, leaving this receptor free to upregulate IL-10. These novel results support the concept of selective TNFR1 blockadein vivoin order that positive anti-inflammatory effects of TNF-αcan be retained via TNFR2 ligation.

scholarly journals 2-Deoxy d-Glucose Prevents Cell Surface Expression of NKG2D Ligands through Inhibition of N-Linked Glycosylation

2012 ◽  
Vol 188 (4) ◽  
pp. 1847-1855 ◽  
Author(s):  
Lars Andresen ◽  
Sarah Line Skovbakke ◽  
Gry Persson ◽  
Michael Hagemann-Jensen ◽  
Karen Aagaard Hansen ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Nkg2d Ligands

scholarly journals Effects of cytokine mixtures on the expression of adhesion molecules in human umbilical vein endothelial cells in an in vitro model of inflammation

2003 ◽  
Vol 22 (3) ◽  
pp. 201-206
Author(s):  
Snezana Markovic ◽  
Andrea Griesmacher ◽  
Alireza Karimi ◽  
Mathias Müller
Keyword(s):  
Endothelial Cells ◽  
Immune System ◽  
Cell Surface ◽  
Adhesion Molecules ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Th2 Cells ◽  
Tnf Alpha ◽  
Specific Cell ◽  
Microvascular Endothelium

As an essential early event in the activation of the immune system increased adherence of circulating neutrophils, lymphocytes and monocytes to the microvascular endothelium is observed. This situation is followed by migration of these cells through vessel walls and their accumulation at sites of tissue injury. This process is mediated by specific cell adhesion molecules being crucial to the generation of immune and inflammatory responses. In this report we demonstrate the effects of cytokine stimulation on endothelial adhesion molecules evoked by incubating HUVECs with two specific cytokine combinations both comprising IL-2, IL-6, IFN-gamma and TNF-alpha, which have been selected because they are elevated in the blood during rejection and infection processes. Combination I additionally include IL-8, which is released by activated monocytes and macrophages and is suggested to be an important angiogenic mediator stimulating the proliferation and migration of endothelial cells. On the other hand combination II contains the two anti-inflammatory cytokines IL-4 and IL-10 which are predominantely synthesized by Th2 cells. While IL-4 demonstrates multiple stimulatory and regulatory effects, IL-10 plays a pivotal part in the regulation of immune responses. Both cytokines block the synthesis of cytokines, such as IL-1, TNF-alpha and IL-12, which are of regulatory importance at the beginning of inflammatory processes. These cytokine mixtures are placed in the center of our studies in order to elucidate their influence on the cell surface expression of a number of adhesion molecules on HUVECs, when combined in multi-component incubation cocktails. The application of these cytokine combinations results in comparable effects significantly increasing the mean fluorescence intensity (MFI) of VCAM-1 slightly up-regulating ICAM-1 surface expression accompanied by the induction of E- and P-selectin expression. These adhesion molecules play pivotal parts in the process of leukocyte transmigration. The experiments reveal a strong up-regulation of these cell surface antigens under conditions mimicking inflammation. This is an essential finding stressing the importance of endothelial cells during the activation of the immune system.

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