Alternatively activated macrophages during parasite infections

Noël, W.; Raes, Geert; Ghassabeh, Gholamreza Hassanzadeh; Baetseĺier, Patrick De; Beck, Alain

doi:10.1016/j.pt.2004.01.004

Cited by 262 publications

(254 citation statements)

References 67 publications

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“…These data suggest that the Th2/Tr1 differentiation as induced by semimature DCs in Th2-cell models results in a balance between an intrinsic inflammation-limiting Tr1 response and the active asthma-promoting Th2-cell response. Interestingly, the upcoming role of such balanced Th2-cell responses in limiting tissue pathology and inflammation has been discussed previously in several infection models and especially for macrophages [74][75][76]. Eur.…”

Section: Discussionmentioning

confidence: 84%

Similar inflammatory DC maturation signatures induced by TNF or Trypanosoma brucei antigens instruct default Th2‐cell responses

Pletinckx

Stijlemans²,

Pavlović

et al. 2011

Eur J Immunol

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DCs represent the major cell type leading to polarized T-helper (Th) cell responses in vivo. Here, we asked whether the instruction of murine Th2 responses by DCs matured with the proinflammatory cytokine TNF is qualitatively different from maturation by different types of TLR4/MyD88-dependent variant-specific surface glycoproteins (VSGs) of Trypanosoma brucei (T. brucei). The results obtained by analyzing DC surface markers, Notch ligand mRNA, cytokines, asthma, and experimental autoimmune encephalomyelitis (EAE) models as well as performing microarrays indicate that both types of stimuli induce similar inflammatory, semi-mature DC profiles. DCs matured by TNF or VSG treatment expressed a common inflammatory signature of 24 genes correlating with their Th2-polarization capacity. However, the same 24 genes and 4498 additional genes were expressed by DCs treated with LPS that went on to induce Th1 cells. These findings support the concept of a default pathway for Th2-cell induction in DCs matured under suboptimal or inflammatory conditions, independent of the surface receptors and signaling pathways involved. Our data also indicate that quantitative differences in DC maturation might direct Th2-vs Th1-cell responses, since suboptimally matured inflammatory DCs induce default Th2-cell maturation, whereas fully mature DCs induce Th1-cell maturation.Key words: DCs . microarray . Th2 cells . TNF . Trypanosoma Supporting Information available online IntroductionDCs play a fundamental role in the induction of adaptive immune responses as well as in the maintenance of peripheral tolerance [1][2][3]. Through the expression of pattern-recognition receptors (PPRs) such as Toll-like receptors (TLRs), DCs are able to sense a wide array of pathogens and mount an appropriate T-helper (Th) cell response [4]. Naïve CD4 1 T-cell precursors can differentiate into a variety of Th-cell lineages characterized by the cytokines produced: Th1 cells secrete predominately IFN-g, Th2 cells release IL-4, IL-5, and IL-13 and Th17 cells typically produce . Although the contribution of DCs for CD4 1 Th-cell polarization is under debate [6], several DC-derived mechanisms have been described to significantly direct Th-cell phenotypes. 3479DCs change their maturation status by upregulating surface expression of MHC class II and costimulatory molecules and by producing a defined set of cytokines to optimally induce distinct Th-cell responses [7][8][9]. Due to their immunostimulatory function, DCs are of particular interest in immunotherapy settings, such as cancer therapy and infectious disease intervention [10,11]. Thus, the Th-cell polarizing profile defined by the maturation signature of DCs is of vital interest. Several membrane markers on DCs and soluble factors secreted by DCs have been described to polarize toward Th2 responses. These include costimulatory molecules such as OX40 [12], , the Notch family member Jagged-2 [14], the cytokine IL-6 [15], or arachidonic acid metabolites such as PGE 2 [16][17][18]. Much less is known about the fac...

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Section: Discussionmentioning

confidence: 84%

Similar inflammatory DC maturation signatures induced by TNF or Trypanosoma brucei antigens instruct default Th2‐cell responses

Pletinckx

Stijlemans²,

Pavlović

et al. 2011

Eur J Immunol

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“…Although many investigations have validated this pathway in multiple immune responses, there are clearly other macrophage populations that exhibit a different phenotype. For example, studies have shown that cancer, asthma, atherosclerosis, and certain infectious processes contain a novel population of ''alternatively activated macrophages,'' or M2 macrophages (45)(46)(47)(48)(49)(50)(51)(52). These macrophages, activated in part by IL-4 and/or IL-13, likely provide the underpinnings for the maintenance of chronic disease via their reported role in regulating specific immune events, promoting fibroblast growth, and angiogenic activities.…”

Section: Mechanisms That Support the Chronicity Of Lung Disease Altermentioning

confidence: 99%

Toll-like Receptors, Notch Ligands, and Cytokines Drive the Chronicity of Lung Inflammation

Raymond

Schaller²,

Hogaboam

et al. 2007

Proceedings of the American Thoracic Society

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“…11,12 Importantly, M1 and M2 are regarded as only two extremes of a continuum of functional stages of macrophages. 11,12 M2 macrophages appear to play a role in tissue repair and parasite defence, 13,14 but exert poor anti-bacterial killing activity. 15 The molecular repertoire of M2 macrophages includes proteins that are expressed at very low levels by classically activated macrophages (M1) including the IL-1 receptor antagonist (IL-1Ra), IL-10 and the mannose receptor (MR) that is involved in the uptake of mannose-containing particles.…”

Section: Introductionmentioning

confidence: 99%

Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production

et al. 2007

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Objective: Obesity is associated with a chronic low-grade inflammation and an increased abundance of macrophages in adipose tissue. Adipose tissue macrophages (ATMs) are assumed to interfere with adipocyte function leading to insulin resistance, thereby contributing to the pathogenesis of type 2 diabetes mellitus. Macrophages exist in separate types of differentiation, but the nature of ATMs is largely unknown. Design and measurements: Stromal vascular cells (SVCs) and ATMs were isolated from human adipose tissues from different locations. We characterized ATMs phenotypically and functionally by flow cytometry, endocytosis assay and determination of secreted cytokines. For comparison, we used macrophages of the 'classical' (M1) and the 'alternative', anti-inflammatory (M2) type differentiated in vitro from peripheral blood monocytes. Results: Like prototypic M2 macrophages, ATMs expressed considerable amounts of mannose receptor, haemoglobin scavenger receptor CD163 and integrin avb5. The number of cells expressing these molecules correlated significantly with the donors' body mass indices (BMIs). Notably, SVCs positive for the common monocyte/macrophage marker CD14 contained a considerable fraction of blood monocytes, the abundance of which did not correlate with the BMIs, pointing to the requirement of the surface markers identified here for the identification of ATMs. ATMs showed endocytic activities similar to M2 macrophages and accordingly secreted high amounts of IL-10 and IL-1 receptor antagonist. However, basal and induced secretion of pro-inflammatory mediators TNF-a, IL-6, IL-1, MCP-1 and MIP-1a was even higher in ATMs than in proinflammatory M1 macrophages. Conclusion: ATMs comprise a particular macrophage type that is M2-like by surface marker expression, but they are competent to produce extensive amounts of inflammatory cytokines, which could considerably contribute to the development of insulin resistance.

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Alternatively activated macrophages during parasite infections

Cited by 262 publications

References 67 publications

Similar inflammatory DC maturation signatures induced by TNF or Trypanosoma brucei antigens instruct default Th2‐cell responses

Similar inflammatory DC maturation signatures induced by TNF or Trypanosoma brucei antigens instruct default Th2‐cell responses

Toll-like Receptors, Notch Ligands, and Cytokines Drive the Chronicity of Lung Inflammation

Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production

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