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 Hepatitis C Virus Inhibits Cell Surface Expression of HLA-DR, Prevents Dendritic Cell Maturation, and Induces Interleukin-10 Production

2008 ◽  
Vol 82 (7) ◽  
pp. 3320-3328 ◽  
Author(s):  
Kousuke Saito ◽  
Malika Ait-Goughoulte ◽  
Steven M. Truscott ◽  
Keith Meyer ◽  
Azra Blazevic ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Cell Surface ◽  
Immune Responses ◽  
Mhc Class Ii ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Hla Dr ◽  
Ifn Γ

ABSTRACT Hepatitis C virus (HCV) chronic infection is characterized by low-level or undetectable cellular immune responses against HCV antigens. HCV proteins have been shown to affect various intracellular events and modulate immune responses, although the precise mechanisms used to mediate these effects are not fully understood. In this study, we have examined the effect of HCV proteins on the modulation of major histocompatibility complex (MHC) class II expression and other functions important for antigen presentation in humans. Expression of an HCV1-2962 genomic clone (HCV-FL) in human fibrosarcoma cells (HT1080) inhibited gamma interferon (IFN-γ)-induced upregulation of human leukocyte antigen-DR (HLA-DR) cell surface expression. Furthermore, inhibition of promoter activities of MHC class II transactivator (CIITA), IFN-γ-activated site (GAS), and HLA-DR was observed in IFN-γ-inducible HT1080 cells expressing HCV-FL by in vitro reporter assays. Exposure of human monocyte-derived dendritic cells (DCs) to cell culture-grown HCV (HCVcc) genotype 1a (clone H77) or 2a (clone JFH1) significantly inhibited DC maturation and was associated with the production of IL-10. Furthermore, DCs exposed to HCVcc were impaired in their functional ability to stimulate antigen-specific CD4-positive (CD4+) and CD8+ T-cell responses. Taken together, our results indicated that HCV can have direct and/or indirect inhibitory effects on antigen-presenting cells, resulting in reduction of antigen-specific T-cell activation. These effects may account for or contribute to the low overall level of immunogenicity of HCV observed in chronically infected patients.

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

Interferon-γ Upregulates CCR5 Expression in Cord and Adult Blood Mononuclear Phagocytes

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1137-1144 ◽  
Author(s):  
Deepa Hariharan ◽  
Steven D. Douglas ◽  
Benhur Lee ◽  
Jian-Ping Lai ◽  
Donald E. Campbell ◽  
...  
Keyword(s):  
Cell Surface ◽  
Hiv Infection ◽  
Chemokine Receptors ◽  
Surface Expression ◽  
Interferon Γ ◽  
Mononuclear Phagocytes ◽  
Cell Surface Expression ◽  
Ccr5 Expression ◽  
Hiv Entry ◽  
Ifn Γ

Abstract The C-C chemokine receptors CCR5 and CCR3 are fusion coreceptors for human immunodeficiency virus (HIV) entry into macrophages. The regulation of their expression influences infectivity by HIV. We report here that interferon-γ (IFN-γ) a cytokine that has bidirectional effects on HIV infection of macrophages, significantly upregulated CCR5 and CCR3 cell surface expression in human mononuclear phagocytes isolated from placental cord blood and adult peripheral blood. Monocytes treated with IFN-γ showed increased chemotaxis to the CCR5 ligands macrophage inflammatory protein-1 (MIP-1) and MIP-1β, confirming the functional relevance of IFN-γ–induced CCR5 expression. However, IFN-γ suppressed HIV entry into macrophages. Interestingly, we demonstrated that IFN-γ inhibited cell surface expression of CD4, the major receptor for HIV. This finding may explain the suppressive effect of IFN-γ on HIV entry into macrophages, despite its enhancing effect on the expression of CCR5 and CCR3 by these cells. In addition, IFN-γ–induced secretion of C-C chemokines (RANTES, MIP-1, and MIP-1β) by mononuclear phagocytes may also suppress HIV entry into macrophages. These data provide further evidence for cytokine-mediated regulation of CCR5 expression and are consistent with a novel paradigm in which cytokines regulate HIV infection and leukocyte migration by reciprocal and opposing effects on the expression of CD4 and chemokine receptors.

In Vitro Infection of Monocytes with HIVBa-L. Effect on Cell Surface Expression of CD4, CD14, HLA-DR, and HLA-DQ

1990 ◽  
Vol 6 (6) ◽  
pp. 731-741 ◽  
Author(s):  
LOYDA M. MELENDEZ-GUERRERO ◽  
JANET K.A. NICHOLSON ◽  
J. STEVEN McDOUGAL
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Hla Dr ◽  
Hla Dq

Interferon-γ Upregulates CCR5 Expression in Cord and Adult Blood Mononuclear Phagocytes

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1137-1144 ◽  
Author(s):  
Deepa Hariharan ◽  
Steven D. Douglas ◽  
Benhur Lee ◽  
Jian-Ping Lai ◽  
Donald E. Campbell ◽  
...  
Keyword(s):  
Cell Surface ◽  
Hiv Infection ◽  
Chemokine Receptors ◽  
Surface Expression ◽  
Interferon Γ ◽  
Mononuclear Phagocytes ◽  
Cell Surface Expression ◽  
Ccr5 Expression ◽  
Hiv Entry ◽  
Ifn Γ

The C-C chemokine receptors CCR5 and CCR3 are fusion coreceptors for human immunodeficiency virus (HIV) entry into macrophages. The regulation of their expression influences infectivity by HIV. We report here that interferon-γ (IFN-γ) a cytokine that has bidirectional effects on HIV infection of macrophages, significantly upregulated CCR5 and CCR3 cell surface expression in human mononuclear phagocytes isolated from placental cord blood and adult peripheral blood. Monocytes treated with IFN-γ showed increased chemotaxis to the CCR5 ligands macrophage inflammatory protein-1 (MIP-1) and MIP-1β, confirming the functional relevance of IFN-γ–induced CCR5 expression. However, IFN-γ suppressed HIV entry into macrophages. Interestingly, we demonstrated that IFN-γ inhibited cell surface expression of CD4, the major receptor for HIV. This finding may explain the suppressive effect of IFN-γ on HIV entry into macrophages, despite its enhancing effect on the expression of CCR5 and CCR3 by these cells. In addition, IFN-γ–induced secretion of C-C chemokines (RANTES, MIP-1, and MIP-1β) by mononuclear phagocytes may also suppress HIV entry into macrophages. These data provide further evidence for cytokine-mediated regulation of CCR5 expression and are consistent with a novel paradigm in which cytokines regulate HIV infection and leukocyte migration by reciprocal and opposing effects on the expression of CD4 and chemokine receptors.

Non-Polarized Cell Surface Expression of Hla-A,B,C and Hla-Dr Antigens in Graves' Thyroid Follicle Cells

Autoimmunity ◽  
1991 ◽  
Vol 10 (3) ◽  
pp. 189-199 ◽  
Author(s):  
Johan Mölne ◽  
Mikael Nilsson ◽  
Svante Jansson ◽  
GÖRan Hansson ◽  
Lars E. Ericson
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Follicle Cells ◽  
Cell Surface Expression ◽  
Thyroid Follicle ◽  
Hla Dr

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 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.

A discrete subpopulation of human monocytes expresses a neutrophil-like proinflammatory (P) phenotype

1994 ◽  
Vol 267 (6) ◽  
pp. L775-L785 ◽  
Author(s):  
C. A. Owen ◽  
M. A. Campbell ◽  
S. S. Boukedes ◽  
R. A. Stockley ◽  
E. J. Campbell
Keyword(s):  
Cell Surface ◽  
Proteinase Inhibitors ◽  
Solid Phase ◽  
Tissue Injury ◽  
Human Leukocyte ◽  
Cell Surface Expression ◽  
Human Monocytes ◽  
Leukocyte Elastase ◽  
Hla Dr ◽  
High Level

We have demonstrated that a discrete and naturally occurring subpopulation of human monocytes expresses a neutrophil-like proinflammatory (P) phenotype. P monocytes constitute 20-30% of the circulating monocyte pool and are characterized by 1) avid adherence to extracellular matrix through high-level cell-surface expression of alpha 5-, beta 1-, and beta 2-integrins; 2) high capacity to produce reactive oxygen species; 3) high content of serine proteinases and alpha 1-proteinase inhibitor; and 4) proteolytic activity against a soluble peptide human leukocyte elastase substrate, [3H]elastin, and solid-phase fibronectin, even in the presence of proteinase inhibitors. However, P monocytes express little or no cell-surface HLA-DR antigen, suggesting that they are unable to participate in specific immune responses. In contrast, the remainder of circulating monocytes have a low proinflammatory potential but contain the population of monocytes with high-level expression of HLA-DR antigen. P monocytes can readily be separated from the remainder of monocytes on the basis of 1) their capacity to adhere to fibronectin; and 2) their absent expression of HLA-DR antigen when flow cytometry or immunomagnetic beads are used. Our data indicate that, when recruited to sites of inflammation, P monocytes can either promote resolution of inflammation or contribute to tissue injury.

Lack of Major Histocompatibility Class II (MHCII) Protein and Decreased Immunosurveillance in Plasmablastic Lymphoma (PBL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5186-5186
Author(s):  
Monika Schmelz ◽  
Santiago Montes-Moreno ◽  
Miguel Piris ◽  
Sarah T Wilkinson ◽  
Lisa M. Rimsza
Keyword(s):  
T Cells ◽  
Cell Surface ◽  
Protein Expression ◽  
B Cell ◽  
Surface Membrane ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Membrane Expression ◽  
Cd8 Cells ◽  
Hla Dr

Abstract Abstract 5186 PBL is a distinct clinicopathological entity classified separately from diffuse large B-cell lymphoma (DLBCL). A recent immunohistochemical (IHC) study described the plasmablastic phenotype of PBL including co-expression of PRDM1/BLIMP1 and XBP1 with lack of the B cell markers PAX5 and CD20. This protein expression profile is unusual for DLBCL and therefore helps to differentiate PBL tumors from conventional DLBCL. In a minority of DLBCL cases, the acquisition of a partial plasmablastic phenotype (Blimp1 positive) is associated with a worse outcome. Given that Blimp1 and MHCII expression are inversely related as normal B cells enter the terminal differentiation program towards plasma cells, and that loss of MHCII mRNA and protein expression correlates with poor outcome DLBCL (likely due to a loss of immunosurveillance), we hypothesized that PBL cases would also lack HLA-DR and have correspondingly low numbers of tumor infiltrating T cells. Twenty-three cases of PBL, which were part of a previously published case series (S. Montes-Moreno et al, Haematologica 2010) from the Spanish National Cancer Research Center were studied with approval of the Carlos III Institutional Review Board. Cases were stained with antibodies specific to HLA-DR and CD8. Three consecutive 60x fields with a minimum of 950 cells were counted per case. As previously (L.M. Rimsza et al, Blood 2004) described, the area of tumor with the lowest frequency of CD8(+) cells was chosen for counting. The IHC results were quantified by counting the number of HLA-DR(+) cells and CD8(+) cells in the total number of malignant cells or lymphoid-appearing cells respectively (obvious stromal and histiocytic cells excluded). HLA-DR staining intensity was also scored as followed: 0 = no staining; 1+ = faint partial staining; 2+ = complete or partial moderate staining; 3+ = complete strong staining. Additionally, HLA-DR staining was characterized as surface membrane, cytoplasmic, or negative. Only three PBL cases (13%) showed the typical B-cell pattern of HLA-DR cell surface membrane expression in a few (2% ± 2) of tumor cells with a faint to partial expression (median intensity of 1.8 ± 0.7), and average of 14% (±10) CD8(+) cells. Cytoplasmic HLA-DR expression in the absence of membrane expression was observed in 10 cases (43.5%) in a minority of cells (9% ±18) with a median intensity of 1.9+ (±0.6), and an average of 10.3% (±6) CD8(+) cells. Ten cases (43.5%) were completely negative for HLA-DR and showed only 7% (± 6) CD8(+) cells. In summary, this study demonstrates the lack of MHCII protein expression on the surface membrane of most cases of PBL, which is associated with a decrease in CD8(+) tumor infiltrating T-cells cells, likely indicative of decreased immunosurveillance. These results are in agreement with our previous studies, in which DLBCL cases showed an average of 11% CD8(+) T-cells in the presence of MHCII cell surface expression, but only 2.8% CD8(+) T-cells in the absence of MHCII protein cell surface expression. The significance of the cytoplasmic localization is not clear, however may represent a stage of partial expression, which is associated with an intermediate level of T cells. Decreased immunosurveillance has long been correlated with deficient host response and tumor containment. The absence of MHCII protein expression may provide a reason for the poor outcome in PBL patients as well as serve as additional tool for diagnosis. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document