Differential Macrophage Polarization in Male and Female BALB/c Mice Infected With Coxsackievirus B3 Defines Susceptibility to Viral Myocarditis

Li, Kang; Xu, Wei; Guo, Qiang; Jiang, Zhenggang; Wang, Ping; Yan, Ye; Xiong, Sidong

doi:10.1161/circresaha.109.195230

Cited by 185 publications

(139 citation statements)

References 35 publications

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“…We have previously reported that the preferential induction of M2 in vivo contributed significantly to the anti-inflammatory functions of IL-33 (8,42). Furthermore, a recent report shows that M2 macrophages are able to promote Treg differentiation in CVB3-induced myocarditis (7). Moreover, it has been shown that Tregs can also induce M2 maturation (43).…”

Section: Discussionmentioning

confidence: 95%

“…Although T lymphocyte responses are required for survival in the early stages of acute pancreatitis, CD4 + T cells can also exacerbate pancreatitis (6). Thus, Th1 cells that produce IFN-g have been associated with the pathogenesis of CVB5-induced pancreatitis (7). In CVB3 infection, the resistance of female mice to myocarditis is associated with the induction of type II cytokines and alternatively activated macrophages (M2) (7).…”

mentioning

confidence: 99%

“…Thus, Th1 cells that produce IFN-g have been associated with the pathogenesis of CVB5-induced pancreatitis (7). In CVB3 infection, the resistance of female mice to myocarditis is associated with the induction of type II cytokines and alternatively activated macrophages (M2) (7). We have previously reported that the recently discovered cytokine, IL-33, is a potent inducer of type II cytokines and M2 (8,9).…”

mentioning

confidence: 99%

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The IL-33/ST2 Pathway Controls Coxsackievirus B5–Induced Experimental Pancreatitis

Sesti-Costa

Silva

Proença-Modena

et al. 2013

The Journal of Immunology

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Coxsackievirus B (CVB) is a common cause of acute and chronic infectious myocarditis and pancreatitis. Th1 cells producing IFN-γ and TNF-α are important for CVB clearance, but they are also associated with the pathogenesis of inflammatory lesions, suggesting that the modulation of Th1 and Th2 balance is likely important in controlling CVB-induced pancreatitis. We investigated the role of IL-33, which is an important recently discovered cytokine for induction of Th2-associated responses, in experimental CVB5 infection. We found that mice deficient in IL-33R, T1/ST2, significantly developed more severe pancreatitis, had greater weight loss, and contained higher viral load compared with wild-type (WT) mice when infected with CVB5. Conversely, WT mice treated with rIL-33 developed significantly lower viral titers, and pancreatitis was attenuated. Mechanistic studies demonstrated that IL-33 enhances the degranulation and production of IFN-γ and TNF-α by CD8+ T and NK cells, which is associated with viral clearance. Furthermore, IL-33 triggers the production of IL-4 from mast cells, which results in enhanced differentiation of M2 macrophages and regulatory T cells, leading to the attenuation of inflammatory pancreatitis. Adoptively transferred mast cells or M2 macrophages reversed the heightened pancreatitis in the T1/ST2−/− mice. In contrast, inhibition of regulatory T cells exacerbated the disease in WT mice. Together, our findings reveal an unrecognized IL-33/ST2 functional pathway and a key mechanism for CVB5-induced pancreatitis. These data further suggest a novel approach in treating virus-induced pancreatitis, which is a major medical condition with unmet clinical needs.

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

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confidence: 99%

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The IL-33/ST2 Pathway Controls Coxsackievirus B5–Induced Experimental Pancreatitis

Sesti-Costa

Silva

Proença-Modena

et al. 2013

The Journal of Immunology

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“…For generation of bone marrow-derived macrophages (BMDMs), bone marrow cells were harvested from uninfected, normal BALB/c mice and filtered through nylon mesh. Bone marrow cells were cultured in L929 cell-conditioned medium at a density of 3 ϫ 10 5 cells/ml of medium and maintained in a 5% CO 2 incubator at 37°C as described previously (46,47). Six days after the initial bone marrow cells culture, the medium was changed and the purity of F4/80 ϩ cells was more than 90%, as determined by flow cytometry (FACSCalibur; BD Biosciences, San Jose, CA).…”

Section: Methodsmentioning

confidence: 99%

DNA-dependent Activator of Interferon-regulatory Factors (DAI) Promotes Lupus Nephritis by Activating the Calcium Pathway

Zhang

Zhou

et al. 2013

Journal of Biological Chemistry

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Background: Macrophage M2b polarization conferred by self-DNA immunization initiates and propagates lupus nephritis. Results: Knockdown of DNA-dependent activator of interferon-regulatory factors (DAI) ameliorates SLE syndrome via blunting macrophage M2b polarization. Conclusion: DAI functions as a DNA sensor in self-DNA-induced macrophage M2b polarization and lupus nephritis. Significance: We disclose the mechanism by which self-DNA induces macrophage M2b polarization and lupus nephritis.

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“…For generation of bone marrow-derived macrophages (BMDMs), bone marrow (BM) cells were harvested from uninfected, normal BALB/c mice and filtered through nylon mesh. BM cells were cultured in L929 cell-conditioned medium at a density of 3 × 10 5 cells/mL of medium and maintained in a 5% CO 2 incubator at 37°C as described previously (Ito et al, 2009;Li et al, 2009). Six days after initial BM cell Figure 4.…”

Section: Cells and Cell Culturementioning

confidence: 99%

C-reactive protein functions as a negative regulator of macrophage activation induced by apoptotic DNA

Zhang

Cai

et al. 2011

Protein Cell

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C-reactive protein (CRP), an acute-phase protein with an ability to bind to nuclear antigen, has been reported to regulate cytokine secretion and modulate immune responses. We previously reported that activated syngeneic lymphocyte-derived apoptotic DNA (apopDNA) could induce macrophage activation and contribute to the initiation and progression of lupus nephritis. It is reasonable to hypothesize that CRP might regulate apopDNA-induced macrophage activation. Herein, CRP was shown to promote macrophage-mediated apopDNA uptake by binding to apopDNA (CRP/apopDNA complex). Notably, CRP/apopDNA treatment inhibited the production of inflammatory cytokines and chemokines by macrophages which could be induced by apopDNA alone. Further coculture and transwell studies revealed that CRP/apopDNA-induced macrophages prohibited apopDNA-induced macrophage activation in an IL-10 dependent manner. These results provide insight into the potential mechanism of CRP regulatory activity in macrophage activation induced by apopDNA in the context of lupus nephritis and other autoimmune diseases.

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Differential Macrophage Polarization in Male and Female BALB/c Mice Infected With Coxsackievirus B3 Defines Susceptibility to Viral Myocarditis

Cited by 185 publications

References 35 publications

The IL-33/ST2 Pathway Controls Coxsackievirus B5–Induced Experimental Pancreatitis

The IL-33/ST2 Pathway Controls Coxsackievirus B5–Induced Experimental Pancreatitis

DNA-dependent Activator of Interferon-regulatory Factors (DAI) Promotes Lupus Nephritis by Activating the Calcium Pathway

C-reactive protein functions as a negative regulator of macrophage activation induced by apoptotic DNA

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