Mannose Receptor (MR) Engagement by Mesothelin GPI Anchor Polarizes Tumor-Associated Macrophages and Is Blocked by Anti-MR Human Recombinant Antibody

Dangaj, Denarda; Abbott, Karen L.; Mookerjee, Ananda; Zhao, Aizhi; Kirby, Pamela S.; Sandaltzopoulos, Raphael; Powell, Daniel J.; Lamazière, Antonin; Siegel, Don L.; Wolf, Claude; Scholler, Nathalie

doi:10.1371/journal.pone.0028386

Cited by 38 publications

(39 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…M2 macrophages have high expression of CD206 (mannose receptor), ARG1 and antiinflammatory cytokines (IL-10, TGF-b) [39,40]. According to these biomarkers, we found that IL-37 shifted iH37Rv-activated macrophages towards an M2 profile.…”

Section: Discussionmentioning

confidence: 75%

IL‐37 Expression is Upregulated in Patients with Tuberculosis and Induces Macrophages Towards an M2‐like Phenotype

et al. 2015

View full text Add to dashboard Cite

Interleukin-37 (IL-37), a member of the IL-1 family, primarily functions as an anti-inflammatory cytokine, reducing inflammation and suppressing the immune response. However, the expression and role of IL-37 in tuberculosis (TB) remains unknown. We aimed to measure serum levels of IL-37 and several important cytokines in 25 patients with active TB and to analyse their association with disease activity. We found that IL-37 levels decreased in patients with TB and recovered after treatment. IL-37 levels negatively correlated with the serum concentration of IFN-c and IL-12 but positively correlated with IL-10 and TGFb levels. After IL-37, secretion was blocked in peripheral blood mononuclear cells from active patients with TB, IFN-c and IL-10 production was significantly upregulated; this was not observed in healthy donors or patients after treatment. IL-37 knockdown significantly enhanced the phagocytic activity of THP1-derived macrophages towards Mycobacterium tuberculosis (M. tb). M1/M2 polarization-associated markers were detected simultaneously, and IL-37 induced a phenotypic shift in THP1-derived macrophages towards a high CD206 + and low CD86 + macrophage subtype. Furthermore, this phenotypic shift was accompanied by upregulated mRNA levels of arginase 1, TGF-b and IL-10, which are characteristic hallmarks of M2 macrophages. In conclusion, our results suggest that increased levels of IL-37 in patients with TB are associated with IFN-c, IL-12, IL-10 and TGF-b levels and that IL-37 plays a pathological role in TB infection by inhibiting the production of pro-inflammatory cytokines and inducing macrophages towards an M2-like phenotype. Thus, IL-37 may be a novel research target to understand the pathogenesis of TB infection.

show abstract

Section: Discussionmentioning

confidence: 75%

IL‐37 Expression is Upregulated in Patients with Tuberculosis and Induces Macrophages Towards an M2‐like Phenotype

et al. 2015

View full text Add to dashboard Cite

show abstract

“…11,29) Transfection of NF-κB (p50) siRNA into M2-like macrophages resulted in a significantly reduction of both of these receptors expression (Fig. 5).…”

Section: Changes In Receptors Expression On the Surface Of M2-like Mamentioning

confidence: 94%

<i>In Vitro</i> Evaluation of Inhibitory Effect of Nuclear Factor-KappaB Activity by Small Interfering RNA on Pro-tumor Characteristics of M2-Like Macrophages

Kono

Kawakami

Higuchi

et al. 2014

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Tumor-associated macrophages (TAMs) have an alternatively activated macrophage phenotype (M2) and promote cancer cell proliferation, angiogenesis and metastasis. Nuclear factor-kappaB (NF-κB) is one of the master regulators of macrophage polarization. Here, we investigated the effect of inhibition of NF-κB activity by small interfering RNA (siRNA) on the pro-tumor response of macrophages located in the tumor microenvironment in vitro. We used mouse peritoneal macrophages cultured in conditioned medium from colon-26 cancer cells as an in vitro TAM model (M2-like macrophages). Transfection of NF-κB (p50) siRNA into M2-like macrophages resulted in a significant decrease in the secretion of interleukin (IL)-10 (a T helper 2 (Th2) cytokine) and a significant increase of T helper 1 (Th1) cytokine production (IL-12, tumor necrosis factor-α, and IL-6). Furthermore, vascular endothelial growth factor production and matrix metalloproteinase-9 mRNA expression in M2-like macrophages were suppressed by inhibition of NF-κB expression with NF-κB (p50) siRNA. In addition, there was a reduction of arginase mRNA expression and increase in nitric oxide production. The cytokine secretion profiles of macrophages cultured in conditioned medium from either B16BL6 or PAN-02 cancer cells were also converted from M2 to classically activated (M1) macrophages by transfection of NF-κB (p50) siRNA. These results suggest that inhibition of NF-κB activity in M2-like macrophages alters their phenotype toward M1.

show abstract

“…Afterwards, these immune cells capture antigen, devour diseased blood cells by participating in receptor-mediated endocytosis and phagocytosis, and play an important biological effects in the maintenance of homeostasis and the body's innate immunity and adaptive immune defense process. [8][9][10][11] In our study, dendritic cell (DC) did not express Fcγ R II in AP-type HI, but highly expressed MR and HLA-DR. At the same time, anti-human IgG immunofluorescence stain also manifested that DC adhered and captured abnormal blood cells.…”

Section: Discussionmentioning

confidence: 56%

Mechanisms of Immune Injury and Heterogeneity of Bone Marrow Hematopoietic Cells Island in Patients with Auto-Immuno-Related Hematocytopenia

Sun

Han

et al. 2014

Journal of Immunoassay and Immunochemistry

View full text Add to dashboard Cite

Because of environmental pollution more and more people are suffered with auto-immuno-related hematocytopenia (AIRH). Serum IL-12, IL-17, and IFN-γ levels were detected by ELISA and lymphocyte subsets were analyzed by flow cytometry. Peroxidase (POX) and HLA-DR of immune cells were detected by cytochemical and immunochemical staining. Cells expressing anti-human IgG, FcγR II, MR, and other molecules in HI were detected by immunofluorescence. Serum IL-12, IL-17, and IFN-γ levels of patients were significantly higher than control group. Lymphocyte subsets of patients showed that the percentages of CD19+ B cells and CD3+ CD8+ T cell in peripheral blood were both significantly elevated. HI were mainly classified into three types, in these three types of hematopoietic cells island, peroxidase, and HLA-DR expression varied. Hematopoietic cells with pathological changes expressed anti-human IgG. The immunocytes with different levels of immunomolecules adhered captured and devoured abnormal hematopoietic cells. Immune cells expressed IL-12, IL-17A, and IL-17RA, leading to inflammatory injury of hematopoietic cells. HI destroys cells which connect auto-antibodies. Immune cells in HI express a variety of immune molecules, promote cell immune responses, and amplify the inflammatory reaction by ADCC effect or phagocytosis. These ultimately destruct directly and damage indirectly hematopoietic cells.

show abstract

Mannose Receptor (MR) Engagement by Mesothelin GPI Anchor Polarizes Tumor-Associated Macrophages and Is Blocked by Anti-MR Human Recombinant Antibody

Cited by 38 publications

References 101 publications

IL‐37 Expression is Upregulated in Patients with Tuberculosis and Induces Macrophages Towards an M2‐like Phenotype

IL‐37 Expression is Upregulated in Patients with Tuberculosis and Induces Macrophages Towards an M2‐like Phenotype

<i>In Vitro</i> Evaluation of Inhibitory Effect of Nuclear Factor-KappaB Activity by Small Interfering RNA on Pro-tumor Characteristics of M2-Like Macrophages

Mechanisms of Immune Injury and Heterogeneity of Bone Marrow Hematopoietic Cells Island in Patients with Auto-Immuno-Related Hematocytopenia

Contact Info

Product

Resources

About