Role of osteopontin in dendritic cell shaping of immune responses

Prete, Annalisa Del; Scutera, Sara; Sozzani, Silvano; Musso, Tiziana

doi:10.1016/j.cytogfr.2019.05.004

Cited by 32 publications

(27 citation statements)

References 129 publications

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“…Consistent with the fact that ECs are not the major cell type producing VEGF[32] Bartonella-triggered angiogenesis has been shown to be supported by VEGF and CXCL8 released by macrophages infiltrating the lesions[8]. Since MSCs are recruited at the sites of infection/inflammation, just in contact with ECs[29,51], we propose thatinfected MSCs might support the angiogenic loop by releasing high levels of pro-angiogenic factors. A role of MSCs can be envisioned in different scenarios of Bartonella infections.…”

supporting

confidence: 67%

Persistent Infection of Human Mesenchymal Stromal Cells With Bartonella Henselae Exerts a Proangiogenic Effect

Scutera¹,

Mitola²,

Sparti³

et al. 2020

Preprint

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Background B henselae is in humans the aetiologic agent of cat-scratch disease and of the vasculoproliferative disorders bacillary angiomatosis and bacillary peliosis. Although endothelial cells are crucial in the pathogenesis other cell types function as reservoir and contribute to pathological angiogenesis. Among them, mesenchymal stromal cells (MSCs) can sense pathogens and mount an appropriate cytokine/chemokine response through different Pattern Recognition Receptors (PRRs). MSCs exert direct antimicrobial effector function but may also shelter bacteria such as M. tuberculosis. Methods Adipose-derived MSCs were infected with B. henselae and analyzed for bacterial persistence by gentamicin protection assay, immunohistochemistry and immunofluorescence. Involvement of PRRs in bacterial infection was evaluated through gene and protein expression analysis. The effect of infection on MSC proliferation, apoptosis and release of soluble factors was assessed. The role of infected-MSC conditioned medium in promoting Bartonella infection of endothelial cells and angiogenesis was demonstrated using respectively gentamicin protection assay and different pro-angiogenic assays including spheroid, wound healing and morphogenesis. Results B. henselae can readily infect MSCs and survive in perinuclear bound vacuoles for up to 8 days. Bartonella infection stimulates MSC proliferation and upregulation of EGFR and of the two pattern recognition receptors (PRRs) TLR2 and NOD1. Specific inhibition of EGFR reduces bacterial internalization and treatment with anti-TLR2 neutralizing antibody or EGFR/NOD1 inhibitors significantly downmodulates CXCL8 production. Secretome analysis shows that, in addition to CXCL8, infected MSCs secrete higher levels of the proangiogenic factors VEGF, FGF-7, MMP-9, PIGF, serpin E1, TSP-1, uPA, IL-6, CCL5 and PDGF-D. Importantly, supernatants from B. henselae-infected MSCs increase the susceptibility of ECs to B. henselae infection while enhancing EC proangiogenic potential. Conclusions Altogether, these findings indicate that MSCs constitute a novel niche for B. henselae, which favors the persistence of vascular proliferative disorders.

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supporting

confidence: 67%

Persistent Infection of Human Mesenchymal Stromal Cells With Bartonella Henselae Exerts a Proangiogenic Effect

Scutera¹,

Mitola²,

Sparti³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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“…In its soluble form, indeed, it is secreted by and also interacts with macrophages and activated leukocytes, reduces the inducible form of NO synthase, promoting inflammation. In its intracellular form, it is expressed by dendritic cells and promotes Th17 and Treg differentiation [94] . Moreover, it is thought to mediate the upregulation of Th1 and Th17 cytokines, mainly IFN-γ and IL-17 [95] , and the inhibition of pro-apoptotic proteins, favoring T cell survival [96] .…”

Section: Osteopontinmentioning

confidence: 99%

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

Toscano¹,

Patti²

2020

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For many years, quantifiable biomarkers in neurological diseases have represented a hot topic. In multiple sclerosis (MS), cerebrospinal fluid biomarkers have played a diagnostic role since the introduction of Poser's criteria in 1983, with IgG oligoclonal bands playing a supporting role in an epoch prior to magnetic resonance imaging and a complementary one after the introduction of McDonald criteria in 2001. Nowadays, that supporting role has turned into a main one in substituting for dissemination in time and defining the diagnosis of MS in patients with a first clinical event, according to the 2017 revised McDonald criteria. Possibly kappa free light chains, N-CAM, chitinase 3-like protein 1 and IgM oligoclonal bands, not yet implemented in clinical practice, could similarly gain importance in the near future. Furthermore, the increasing knowledge of molecular mechanisms leading to chronic inflammation has enhanced interest in looking for biomarkers of disease activity, better defining the MS phenotype and patients with highly active disease. Accordingly, myelin proteins, intermediate filaments, metalloproteinases and other molecules involved in the inflammatory cascade, are currently under investigation. Finally, it has long been known that axonal loss occurs from the early phases, leading to a progressive neurological deterioration. Since established criteria to assess treatment failure and transition to progressive forms are still lacking, both treatment response and prognostic biomarkers would be useful to predict MS course, and neurofilaments seem to have this potential. The purpose of this review article was to illustrate biomarkers that have been already validated or require further validation after proving to be useful in exploratory studies and potentially could prove useful in clinical practice in the coming years.

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“…More importantly, in the context of the present review, Tα1 bone marrow cultures up-regulated osteopontin (OPN) during differentiation and upon stimulation with microbial agonists. OPN has been the subject of intense research in cancer (105), and a wealth of evidence has been provided to demonstrate that OPN, secreted by tumor cells as well as infiltrating immune cells, promotes tumor growth and metastasis by supporting a pro-tumorigenic environment (105). However, OPN is present in both secreted and intracellular forms, and the functions may be different (106).…”

Section: Novel Concepts In Cancer Immunotherapy Open New Opportunitiementioning

confidence: 99%

A Reappraisal of Thymosin Alpha1 in Cancer Therapy

et al. 2019

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Thymosin alpha1 (Tα1), an endogenous peptide first isolated from the thymic tissue in the mid-sixties, has gained considerable attention for its immunostimulatory activity that led to its application to diverse pathological conditions, including cancer. Studies in animal models and human patients have shown promising results in different types of malignancies, especially when Tα1 was used in combination with other chemo- and immune therapies. For this reason, the advancements in our knowledge on the adjuvant role of Tα1 have moved in parallel with the development of novel cancer therapies in a way that Tα1 was integrated to changing paradigms and protocols, and tested for increased efficacy and safety. Cancer immunotherapy has recently experienced a tremendous boost following the development and clinical application of immune checkpoint inhibitors. By unleashing the full potential of the adaptive immune response, checkpoint inhibitors were expected to be very effective against tumors, but it soon became clear that a widespread and successful application was not straightforward and shortcomings in efficacy and safety clearly emerged. This scenario led to the development of novel concepts in immunotherapy and the design of combination protocols to overcome these limitations, thus opening up novel opportunities for Tα1 application. Herein, we summarize in a historical perspective the use of Tα1 in cancer, with particular reference to melanoma, hepatocellular carcinoma and lung cancer. We will discuss the current limitations of checkpoint inhibitors in clinical practice and the mechanisms at the basis of a potential application of Tα1 in combination protocols.

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Role of osteopontin in dendritic cell shaping of immune responses

Cited by 32 publications

References 129 publications

Persistent Infection of Human Mesenchymal Stromal Cells With Bartonella Henselae Exerts a Proangiogenic Effect

Persistent Infection of Human Mesenchymal Stromal Cells With Bartonella Henselae Exerts a Proangiogenic Effect

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

A Reappraisal of Thymosin Alpha1 in Cancer Therapy

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