Characteristics of Suppressor Macrophages Induced by Mycobacterial and Protozoal Infections in relation to Alternatively Activated M2 Macrophages

Tomioka, Haruaki; Tatano, Yutaka; Maw, Win Win; Sano, Chiaki; Kanehiro, Yuichi; Shimizu, Toshiaki

doi:10.1155/2012/635451

Cited by 52 publications

(60 citation statements)

References 101 publications

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“…5). This mode of gene expression is clearly distinguishable from those of typical M1 MΦs and M2 MΦs23527. Notably, MIS-MΦs show high-level expression of CCR7 and some M2 MΦ-specific IL-10, Ym1, and CD163 genes (Fig.…”

Section: Discussionmentioning

confidence: 86%

Unique Macrophages Different from M1/M2 Macrophages Inhibit T Cell Mitogenesis while Upregulating Th17 Polarization

Tatano

Shimizu

Tomioka

2014

Sci Rep

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Mycobacterial infection induces suppressor macrophages (MΦs), causing disease exacerbation. There are two major MΦ subsets (M1 and M2 MΦs) that are phenotypically and functionally different. Here, we examined which of the MΦ subsets the mycobacterial infection-induced suppressor MΦs (MIS-MΦs) belong to. MIS-MΦs down-regulated T cell production of Th1 and Th2 cytokines but markedly increased production of interleukin (IL)-17A and IL-22 through up-regulation of Th17 cell expansion. In this phenomenon, a novel MΦ population, which is functionally distinguishable from M1 and M2 MΦ subsets and possesses unique phenotypes (IL-12+, IL-1βhigh, IL-6+, tumor necrosis factor (TNF)-α+, nitric oxide synthase (NOS) 2+, CCR7high, IL-10high, arginase (Arg)-1−, mannose receptor (MR)low, Ym1high, Fizzlow, and CD163high), played central roles through the action of IL-6 and transforming growth factor (TGF)-β but not IL-21 and IL-23. This new type of MΦ population was induced in infected mice and actively supported the in vivo expansion of Th17 cells.

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Section: Discussionmentioning

confidence: 86%

Unique Macrophages Different from M1/M2 Macrophages Inhibit T Cell Mitogenesis while Upregulating Th17 Polarization

Tatano

Shimizu

Tomioka

2014

Sci Rep

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“…The results suggested that IL‐17A −/− mice with ROP expressed relatively low levels of inflammatory cytokines with statistical significance compared with WT controls (MCP‐1, intercellular adhesion molecule 1, VEGF, TNF‐ α , inducible nitric oxide synthase, interferon‐ γ , IL‐1 β , IL‐6, Toll‐like receptor 4 and IL‐12), indicating potential roles of IL‐17A in M1 polarization. Also, according to the functional profiles of M1 and M2 macrophages introduced by Haruaki Tomioka et al . and the findings we detected, significant high levels of Fizz1, transforming growth factor‐ β , IL‐1RA and CD206, and low levels of TNF‐ α , MHC II and IL‐6 at P17 suggested a predominant mixed M2a and M2c phenotype in IL‐17A deficiency (Table ).…”

Section: Resultsmentioning

confidence: 99%

“…As a result, it is preferable that signatures of macrophage subtypes may not exclude one another but display an overlapping effect. Based on the data presented and the functional profiles of M1 and M2 macrophages introduced by Haruaki Tomioka et al ., the study believed that IL‐17A neutralization alleviated inflammation and facilitated tissue repair in ocular NV by modulating macrophage polarization toward the M2 phenotype and reduced expression of VEGF from M1 macrophages.…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐17A neutralization alleviated ocular neovascularization by promoting M2 and mitigating M1 macrophage polarization

et al. 2016

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SummaryNeovascularization (NV), as a cardinal complication of several ocular diseases, has been intensively studied, and research has shown its close association with inflammation and immune cells. In the present study, the role of interleukin-17A (IL-17A) in angiogenesis in the process of ocular NV both in vivo and in vitro was investigated. Also, a paracrine role of IL-17A was demonstrated in the crosstalk between endothelial cells and macrophages in angiogenesis. In the retinas of mice with retinopathy of prematurity, the IL-17A expression increased significantly at postnatal day 15 (P15) and P18 during retinal NV. Mice given IL-17A neutralizing antibody (NAb) developed significantly reduced choroidal NV and retinal NV. Studies on vascular endothelial growth factor (VEGF) over-expressing mice suggested that IL-17A modulated NV through the VEGF pathway. Furthermore, IL-17A deficiency shifted macrophage polarization toward an M2 phenotype during retinal NV with significantly reduced M1 cytokine expression compared with wild-type controls. In vitro assays revealed that IL-17A treated macrophage supernatant gave rise to elevated human umbilical vascular endothelial cell proliferation, tube formation and VEGF receptor 1 and receptor 2 expression. Therefore, IL-17A could potentially serve as a novel target for treating ocular NV diseases. The limitation of this study involved the potential mechanisms, such as which transcription accounted for macrophage polarization and how the subsequent cytokines were modulated when macrophages were polarized. Further studies need to be undertaken to definitively determine the extent to which IL-17A neutralizing anti-angiogenic activity depends on macrophage modulation compared with anti-VEGF treatment.

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“…They also efficiently produce other cytokines, including IL-1b, TNF-a, and IL-6, and participate as inducers as well as effector cells in polarized Th1 responses, and mediate resistance against intracellular parasites and tumors. 25 As such, for comparison and appropriate clarification of the roles of M2 macrophages in cellular transitions and other cell activities, native and M1macrophages should be included to rule out the influence of these macrophage types in such processes.…”

Section: M2-polarized Tams Promoted Emt Of Pancreatic Cancer Cells C-mentioning

confidence: 99%

M2-polarized tumor-associated macrophages promoted epithelial–mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway

Liu

Shi

et al. 2013

Laboratory Investigation

383

290

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M2-polarized tumor-associated macrophages (TAMs) are key regulators of the link between inflammation and cancer. A negative correlation between infiltration intensity of M2-polarized TAMs and prognosis of pancreatic cancer has been reported. Epithelial-mesenchymal transition (EMT) is an important biological process in the progression of primary tumors toward metastasis. Inflammation-induced EMT has been previously shown, therefore, we hypothesized M2-polarized TAMs could induce EMT in pancreatic cancer. Toll-like receptor 4 (TLR4) signaling has an active role in tumor progression during chronic inflammation and the receptor is primarily expressed on macrophages. Activation of TLR4 on M2-polarized TAMs stimulates an increase in the cytokine interleukin-10 (IL-10); consequently, another aim was to investigate the potential role of TLR4/IL-10 signaling in the EMT of pancreatic cancer. Treatment with IL-4 (20 ng/ml) for 24 h successfully induced the polarization of macrophage cell line RAW 264.7 to M2 phenotype, IL-10 high , IL-12 low , and IL-23 low , and high expression of CD204 and CD206. A coculture system allowed investigation of the roles of M2-polarized TAMs and TLR4/IL-10 signaling in the EMT of Panc-1 and BxPC-3 pancreatic cancer cell lines. Our results showed that coculture with M2-polarized TAMs increased fibroblastic morphology, upregulated mesenchymal markers vimentin and snail at the mRNA and protein levels, and increased proliferation, migration, and metalloproteinase (MMP)2 and MMP9 proteolytic activity in pancreatic cancer cells. Simultaneously, coculture with M2-polarized TAMs decreased the expression of the epithelial marker E-cadherin. Coculture with pancreatic cancer cells increased TLR4 mRNA and protein expression in M2-polarized TAMs. Application of TLR4 siRNA and neutralizing antibodies against TLR4 and IL-10 markedly inhibited E-cadherin reduction and the upregulation of snail and vimentin. Furthermore, activation of TLR4 signaling by lipopolysaccharide profoundly increased the EMT of pancreatic cancer cells. In conclusion, M2-polarized TAMs promoted EMT in pancreatic cancer cells partially through TLR4/IL-10 signaling, suggesting novel therapeutic strategies and enhancing our understanding of M2-polarized TAMs. Pancreatic ductal adenocarcinoma is highly malignant and is resistant to chemo-and radiotherapeutics. 1 Recent evidence suggests the inflammatory environment of the tumor is critical for its progression. 2 Tumor-associated macrophages (TAMs) are derived from circulating monocytes, which are highly abundant within the tumor and provide a key link between inflammation and cancer. 3 TAMs develop a phenotype similar to M2-polarized macrophages and respond to recruitment to the tumor microenvironment. 4 Previous studies have commonly associated elevated numbers of TAMs with tumor progression and poor patient outcome. 5 This association is likely linked to the typical presence of M2-polarized TAMs during cancer invasion, 6 however, the exact mechanisms by which these cells influence the pr...

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Characteristics of Suppressor Macrophages Induced by Mycobacterial and Protozoal Infections in relation to Alternatively Activated M2 Macrophages

Cited by 52 publications

References 101 publications

Unique Macrophages Different from M1/M2 Macrophages Inhibit T Cell Mitogenesis while Upregulating Th17 Polarization

Unique Macrophages Different from M1/M2 Macrophages Inhibit T Cell Mitogenesis while Upregulating Th17 Polarization

Interleukin‐17A neutralization alleviated ocular neovascularization by promoting M2 and mitigating M1 macrophage polarization

M2-polarized tumor-associated macrophages promoted epithelial–mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway

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