Differentiation of C2D Macrophage Cells after Adoptive Transfer

Potts, Betsey E.; Hart, Marcia L.; Snyder, Laura; Boyle, Dan; Mosier, Derek A.; Chapes, Stephen K.

doi:10.1128/cvi.00328-07

Cited by 19 publications

(27 citation statements)

References 67 publications

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“…Importantly, the Mreg characterized in our studies efficiently interferes with distinct inflammatory reactions after adoptive transfer and induces the production of IL-10 by CD4 + T cells in vivo, as well as in cultures of Ag-specific stimulated CD4 + T in vitro. Our findings are in line with several studies that demonstrate the longevity of macrophages and their immunosuppressive potential (22,23,41,42). Yet, to our knowledge, this is the first study to characterize a macrophage population induced by a single pathogen-derived immunomodulator that exerts immunosuppressive activities in unrelated inflammatory settings.…”

Section: Discussionsupporting

confidence: 81%

A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation

Ziegler

Rausch

Steinfelder

et al. 2015

The Journal of Immunology

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Immunomodulation is a common feature of chronic helminth infections and mainly attributed to the secretion of bioactive molecules, which target and modify host immune cells. In this study, we show that the helminth immunomodulator AvCystatin, a cysteine protease inhibitor, induces a novel regulatory macrophage (Mreg; AvCystatin-Mreg), which is sufficient to mitigate major parameters of allergic airway inflammation and colitis in mice. A single adoptive transfer of AvCystatin-Mreg before allergen challenge suppressed allergen-specific IgE levels, the influx of eosinophils into the airways, local and systemic Th2 cytokine levels, and mucus production in lung bronchioles of mice, whereas increasing local and systemic IL-10 production by CD4+ T cells. Moreover, a single administration of AvCystatin-Mreg during experimentally induced colitis strikingly reduced intestinal pathology. Phenotyping of AvCystatin-Mreg revealed increased expression of a distinct group of genes including LIGHT, sphingosine kinase 1, CCL1, arginase-1, and costimulatory molecules, CD16/32, ICAM-1, as well as PD-L1 and PD-L2. In cocultures with dendritic cells and CD4+ T cells, AvCystatin-Mreg strongly induced the production of IL-10 in a cell-contact–independent manner. Collectively, our data identify a specific suppressive macrophage population induced by a single parasite immunomodulator, which protects against mucosal inflammation.

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Section: Discussionsupporting

confidence: 81%

A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation

Ziegler

Rausch

Steinfelder

et al. 2015

The Journal of Immunology

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“…C2D macrophages cultured in vitro express low levels of Mac-2 and Ly-6C, and almost no CD11b, indicative of an immature macrophage phenotype (28,29). We observed no changes in any of the three cell surface markers on C2D macrophages cocultured with preadipocytes ( Fig.…”

Section: Vol 17 2010 Macrophage-adipocyte Interactions 653mentioning

confidence: 69%

“…To test this hypothesis, we performed the experiment with the C2D macrophage line (3,28,29). C2D macrophages have an early macrophage lineage phenotype when grown in vitro.…”

Section: Vol 17 2010 Macrophage-adipocyte Interactions 653mentioning

confidence: 99%

Interactive Changes between Macrophages and Adipocytes

Xie

Ortega

Mora

et al. 2010

Clin Vaccine Immunol

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Obesity is associated with a proinflammatory state, with macrophage infiltration into adipose tissue. We tested the hypothesis that communication between macrophages and adipocytes affects insulin resistance by disrupting insulin-stimulated glucose transport, adipocyte differentiation, and macrophage function. To test this hypothesis, we cocultured 3T3-L1 adipocytes with C2D macrophages or primary peritoneal mouse macrophages and examined the impacts of macrophages and adipocytes on each other. Adipocytes and preadipocytes did not affect C2D macrophage TNF-␣, IL-6, or IL-1␤ transcript concentrations relative to those obtained when C2D macrophages were incubated alone. However, preadipocytes and adipocytes increased PEC-C2D macrophage IL-6 transcript levels, while preadipocytes inhibited IL-1␤ transcript levels compared to those obtained when PEC-C2D macrophages were incubated in medium alone. We found that adipocyte coculture increased macrophage consumption of tumor necrosis factor alpha (TNF-␣), interleukin 1␤ (IL-1␤), and, in some cases, IL-6. C2D macrophages increasingly downregulated GLUT4 transcript levels in differentiated adipocytes. Recombinant TNF-␣, IL-1␤, and IL-6 also downregulated GLUT4 transcript levels relative to those for the control. However, only IL-6 was inhibitory at concentrations detected in macrophage-adipocyte cocultures. IL-6 and TNF-␣, but not IL-1␤, inhibited Akt phosphorylation within 15 min of insulin stimulation, but only IL-6 was inhibitory 30 min after stimulation. Lastly, we found that adipocyte differentiation was inhibited by macrophages or by recombinant TNF-␣, IL-6, and IL-1␤, with IL-6 having the most impact. These data suggest that the interaction between macrophages and adipocytes is a complex process, and they support the hypothesis that the macrophage-adipocyte interaction affects insulin resistance by disrupting insulin-stimulated glucose transport, adipocyte differentiation, and macrophage function.

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“…C2D macrophage cells reside early in the macrophage lineage in vitro , but differentiate to a more mature, phenotype after adoptive transfer to the peritoneal cavity (PEC-C2D) [15]. These macrophage cells differentiate and traffic like primary macrophages and can provide insight into macrophage function [16].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of macrophage plasticity in brown and white adipose tissue

Ortega

Xie

Mora

et al. 2011

Cellular Immunology

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There are still questions about whether macrophage differentiation is predetermined or is induced in response to tissue microenvironments. C2D macrophage cells reside early in the macrophage lineage in vitro, but differentiate to a more mature phenotype after adoptive transfer to the peritoneal cavity (PEC-C2D). Since C2D macrophage cells also traffic to adipose tissue after adoptive transfer, we explored the impact of white adipose tissue (WAT), brown adipose tissue (BAT) and in vitro cultured adipocytes on C2D macrophage cells. When PEC-C2D macrophage cells were cultured with preadipocytes the cells stretched out and CD11b and Mac-2 expression was lower compared to PEC-C2D macrophage cells placed in vitro alone. In contrast, PEC-C2D cells co-cultured with adipocytes maintained smaller, round morphology and more cells expressed Mac-2 compared to PEC-C2D co-cultured with preadipocytes. After intraperitoneal injection, C2D macrophage cells migrated into both WAT and BAT. A higher percentage of C2D macrophage cells isolated from WAT (WAT-C2D) expressed Ly-6C (33%), CD11b (11%), Mac-2 (11%) and F4/80 (29%) compared to C2D macrophage cells isolated from BAT (BAT-C2D). Overall, BAT-C2D macrophage cells had reduced expression of many cytokine, chemokine and receptor gene transcripts when compared to in vitro grown C2D macrophages, while WAT-C2D macrophage cells and PEC-C2D up-regulated many of these gene transcripts. These data suggest that the C2D macrophage phenotype can change rapidly and distinct phenotypes are induced by different microenvironments.

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Differentiation of C2D Macrophage Cells after Adoptive Transfer

Cited by 19 publications

References 67 publications

A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation

A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation

Interactive Changes between Macrophages and Adipocytes

Evaluation of macrophage plasticity in brown and white adipose tissue

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