HLA-G Molecules in Autoimmune Diseases and Infections

Rizzo, Roberta; Bortolotti, Daria; Bolzani, Silvia; Fainardi, Enrico

doi:10.3389/fimmu.2014.00592

Cited by 110 publications

(102 citation statements)

References 160 publications

(156 reference statements)

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“…The results obtained suggest HLA-G as a mechanism of immune privilege that creates a protected niche for a bacterial reservoir, similar to the role of HLA-G molecules during viral infections (16). This hypothesis is in agreement with the previous observations on the implications of HLA-G expression in bacterial infections.…”

Section: Discussionsupporting

confidence: 82%

“…HLA-G is involved in mechanisms of immune tolerance under several conditions, including pregnancy, organ transplantation, and autoimmune and inflammatory diseases by inhibiting cytolytic functions of natural killer cells, cytotoxic T lymphocytes, and T and dendritic cells, as well as by inhibiting alloproliferative responses (16). Both soluble and membrane-bound HLA-G isoforms have similar functions and interact with specific inhibitory receptors (ILT-2 and ILT-4) expressed by immune cells.…”

mentioning

confidence: 99%

“…Both soluble and membrane-bound HLA-G isoforms have similar functions and interact with specific inhibitory receptors (ILT-2 and ILT-4) expressed by immune cells. During viral infections, HLA-G molecules are upregulated by the virus as a mechanism of immune escape (16), inhibiting the host immune response. Few data are available on the effect of bacterial infections on HLA-G expression.…”

mentioning

confidence: 99%

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Pseudomonas aeruginosa Quorum Sensing Molecule N -(3-Oxododecanoyl)- l -Homoserine-Lactone Induces HLA-G Expression in Human Immune Cells

et al. 2015

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c HLA-G is a nonclassical class I human leukocyte antigen (HLA) involved in mechanisms of immune tolerance. The objective of this study was to determine whether N-(3-oxododecanoyl)-L-homoserine lactone (3O-C 12 -HSL), a quorum sensing molecule produced by Pseudomonas aeruginosa, could modify HLA-G expression to control the host immune response. We evaluated the ability of 3O-C 12 -HSL to induce HLA-G expression in primary immune cells, monocytes (U937 and THP1), and T-cell lines (Jurkat) in vitro and analyzed the cellular pathway responsible for HLA-G expression. We studied the HLA-G promoter with a luciferase assay and interleukin-10 (IL-10) and p38/CREB signaling with enzyme-linked immunosorbent assay and immunofluorescence, respectively. We observed that 3O-C 12 -HSL is able to induce HLA-G expression in human monocytes and T cells. We showed that the induction of HLA-G by 3O-C 12 -HSL is p38/CREB and IL-10 dependent. 3O-C 12 -HSL treatment is able to arrest only the U937 cell cycle, possibly due to the peculiar expression of the ILT2 receptor in the U937 cell line. Our observations suggest HLA-G as a mechanism to create a protected niche for the bacterial reservoir, similar to the role of HLA-G molecules during viral infections. Bacterial diseases can result in serious or life-threatening complications, such as bacteremia, kidney failure, and toxic shock syndrome. For this, the fight against bacterial infection represents one of the high points of modern medicine. Lack of progress in controlling mortality and morbidity associated with severe bacterial infections in part reflects our limited understanding of the complex biological pathways that bacteria use to regulate host immune response. Many bacteria are capable of forming a wellorganized bacterial population during host infection, and Pseudomonas aeruginosa is one of the most commonly studied. As the cell population increases, P. aeruginosa increases the expression of quorum sensing (QS) molecules that bind to the transcriptional activators, enabling the expression of target genes involved in P. aeruginosa virulence (1). P. aeruginosa has two well-studied QS systems, las and rhl (2-4). The las system consists of the LasR transcriptional regulator and the LasI synthase protein, which is essential for the production of the signal molecule N-(3-oxododecanoyl)-L-homoserine lactone (3O-C 12 -HSL) that also is required for LasR activation (4). Recent studies have shown that 3O-C 12 -HSL has the potential to modify the functions of host immune cells (5-9). In particular, 3O-C 12 -HSL inhibits professional immune cells, such as dendritic and T cells (10), promotes immune cell apoptosis (11-13), and blocks the response of macrophages and monocytes to toll-like receptor (TLR) signals (14). However, the mechanism of this immune-regulatory activity has yet to be fully characterized.HLA-G is a nonclassical class I human leukocyte antigen (HLA) characterized by the presence of membrane-bound (G1-G4) and soluble (G5-G7) isoforms (15). HLA-G is involved in mechanisms of...

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Section: Discussionsupporting

confidence: 82%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Pseudomonas aeruginosa Quorum Sensing Molecule N -(3-Oxododecanoyl)- l -Homoserine-Lactone Induces HLA-G Expression in Human Immune Cells

et al. 2015

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“…P2X7 receptors mediate transforming growth factor β secretion. P2X7 receptor activation also releases a potent immunosuppressive agent, HLA-G [66,67] and vascular endothelial growth factor, another major player in inflammation [68]. Another function of P2X7 receptors in inflammation is the activation of transcription factors such as NFkB and NFAT [69,70].…”

Section: Inflammation and P2x Receptorsmentioning

confidence: 99%

P2X ion channel receptors and inflammation

Burnstock

2016

Purinergic Signalling

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Neuroinflammation limits tissue damage in response to pathogens or injury and promotes repair. There are two stages of inflammation, initiation and resolution. P2X receptors are gaining attention in relation to immunology and inflammation. The P2X7 receptor in particular appears to be an essential immunomodulatory receptor, although P2X1 and P2X4 receptors also appear to be involved. ATP released from damaged or infected cells causes inflammation by release of inflammatory cytokines via P2X7 receptors and acts as a danger signal by occupying upregulated P2X receptors on immune cells to increase immune responses. The purinergic involvement in inflammation is being explored for the development of novel therapeutic strategies.

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“…The role of HLA-G has been widely elucidated in a multitude of pathological scenarios as described above, selected viral and parasitic infections and in septic shock [25][26][27][28]. However, its role in chronic bacterial infections, most importantly, tuberculosis, is yet to be determined.…”

Section: Introductionmentioning

confidence: 98%