Monocyte Responses in the Context of Q Fever: From a Static Polarized Model to a Kinetic Model of Activation

Mehraj, Vikram; Textoris, Julien; Amara, Amira Ben; Ghigo, Éric; Raoult, Didier; Capo, Christian; Mège, Jean‐Louis

doi:10.1093/infdis/jit266

Cited by 29 publications

(45 citation statements)

References 29 publications

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“…In contrast, EXT1 was largely not regulated in M2-like macrophages from patients with chronic lung diseases such as asthma and COPD, 50,52 and was downregulated in macrophages in murine obesity models. 58,59 However, EXT2 appeared to be unregulated or decreased by M1 polarization [40][41][42][43] and in RA. 47 Changes in EXT2 expression may have more limited effects on HS structure as EXT2 is normally produced in excess.…”

Section: Ext1 and Ext2mentioning

confidence: 92%

“…3). 40,41 Increased expression of EXT1 in pro-inflammatory environments may imply that HS chain elongation is stimulated by pro-inflammatory signals. In support of this, HS chain length is also increased by pro-inflammatory cytokines Enzymes responsible for HS biosynthesis.…”

Section: Ext1 and Ext2mentioning

confidence: 99%

“…82 It is highly probable that GLCE also affects binding and signaling in macrophages, as all the characterized protein binding HS-sites contain at least one IdoA. 39 46 The expression of HS2ST1, HS3ST1, HS3ST2, and HS6ST1 is dramatically downregulated up to 12.5-fold in human and murine M1 macrophages in vitro, [40][41][42]44,45 strongly suggesting an anti-inflammatory role of O-sulfation. In line with these studies, HS2ST1, HS3ST1, HS3ST2, and HS6ST1 are also decreased up to 100-fold in macrophages from M1-driven diseases such as RA, 47,48 while their expression is increased in macrophages from more M2-associated diseases, such as asthma and COPD.…”

Section: D-glucuronyl C5-epimerasementioning

confidence: 99%

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Effect of Polarization and Chronic Inflammation on Macrophage Expression of Heparan Sulfate Proteoglycans and Biosynthesis Enzymes

Swart

Troeberg

2018

J Histochem Cytochem.

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Heparan sulfate (HS) proteoglycans on immune cells have the ability to bind to and regulate the bioactivity more than 400 bioactive protein ligands, including many chemokines, cytokines, and growth factors. This makes them important regulators of the phenotype and behavior of immune cells. Here we review how HS biosynthesis in macrophages is regulated during polarization and in chronic inflammatory diseases such as rheumatoid arthritis, atherosclerosis, asthma, chronic obstructive pulmonary disease and obesity, by analyzing published micro-array data and mechanistic studies in this area. We describe that macrophage expression of many HS biosynthesis and core proteins is strongly regulated by macrophage polarization, and that these expression patterns are recapitulated in chronic inflammation. Such changes in HS biosynthetic enzyme expression are likely to have a significant impact on the phenotype of macrophages in chronic inflammatory diseases by altering their interactions with chemokines, cytokines, and growth factors. (J Histochem Cytochem 67:9-27, 2019)

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Section: Ext1 and Ext2mentioning

confidence: 92%

Section: Ext1 and Ext2mentioning

confidence: 99%

Section: D-glucuronyl C5-epimerasementioning

confidence: 99%

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Effect of Polarization and Chronic Inflammation on Macrophage Expression of Heparan Sulfate Proteoglycans and Biosynthesis Enzymes

Swart

Troeberg

2018

J Histochem Cytochem.

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“…The datasets included were RNA-sequencing (RNA-seq) results generated by our laboratory (temporary ID: PRJNA339309), 13 the dataset publicly available as GSE57614, 14 and the dataset publicly available as GSE36537. 15 Brief experimental details for each of the datasets are listed in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Deconvolution of heterogeneous wound tissue samples into relative macrophage phenotype compositionviamodels based on gene expression

Ferraro

Dampier

Weingarten

et al. 2017

Integrative Biology

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Macrophages, the primary cell of the innate immune system, act on a spectrum of phenotypes that correspond to diverse functions. Dysregulation of macrophage phenotype is associated with many diseases. In particular, defective transition from pro-inflammatory (M1) to anti-inflammatory (M2) behavior has been implicated as a potential source of sustained inflammation that prevents healing of chronic wounds such as diabetic ulcers. In order to design effective treatments, an understanding of the relative presence of macrophage phenotypes during tissue repair is necessary. Inferring the relative phenotype composition is currently challenging due to the heterogeneous nature of the macrophages themselves and also of tissue samples. We propose here a method to deconvolute gene expression from heterogeneous tissue samples into the composition of two primary macrophage phenotypes (M1 and M2). Our final method uses gene expression signatures for each phenotype cultivated in vitro as input to a predictive model that infers sample composition with an average error of 0.16, and whose predictions fit known compositions prepared in vitro with an R2 value of 0.90. Finally, we apply this model to describe macrophage behavior in human diabetic ulcer healing using clinically isolated ulcer tissue samples. The model predicted that non-healing diabetic ulcers contained higher proportions of M1 macrophages compared to healing diabetic ulcers, in agreement with numerous studies that have implicated a dysfunctional M1-to-M2 transition in the impaired healing of diabetic ulcers. These results show proof of concept that the model holds utility in making predictions regarding macrophage behavior in heterogeneous samples, with potential application as a wound healing diagnostic.

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“…To assess the mechanisms underlying the permissiveness of AMs to C. burnetii, we evaluated M1/M2 polarization, which has previously been shown to be important for C. burnetii replication and pathogenesis (24,25). Initially, we evaluated the expression of genes known to be hallmarks of M1 and M2 polarization in AMs and BMDMs.…”

Section: Resultsmentioning

confidence: 99%

Murine Alveolar Macrophages Are Highly Susceptible to Replication of Coxiella burnetii Phase IIIn Vitro

et al. 2016

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bCoxiella burnetii is a Gram-negative bacterium that causes Q fever in humans. Q fever is an atypical pneumonia transmitted through inhalation of contaminated aerosols. In mammalian lungs, C. burnetii infects and replicates in several cell types, including alveolar macrophages (AMs). The innate immunity and signaling pathways operating during infection are still poorly understood, in part because of the lack of relevant host cell models for infection in vitro. In the study described here, we investigated and characterized the infection of primary murine AMs by C. burnetii phase II in vitro. Our data reveal that AMs show a pronounced M2 polarization and are highly permissive to C. burnetii multiplication in vitro. Murine AMs present an increased susceptibility to infection in comparison to primary bone marrow-derived macrophages. AMs support more than 2 logs of bacterial replication during 12 days of infection in culture, similar to highly susceptible host cells, such as Vero and THP-1 cells. As a proof of principle that AMs are useful for investigation of C. burnetii replication, we performed experiments with AMs from Nos2 ؊/؊ or Ifng ؊/؊ mice. In the absence of gamma interferon and nitric oxide synthase 2 (NOS2), AMs were significantly more permissive than wild-type cells. In contrast, AMs from Il4 ؊/؊ mice were more restrictive to C. burnetii replication, supporting the importance of M2 polarization for the permissiveness of AMs to C. burnetii replication. Collectively, our data account for understanding the high susceptibility of alveolar macrophages to bacterial replication and support the use of AMs as a relevant model of C. burnetii growth in primary macrophages.

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Monocyte Responses in the Context of Q Fever: From a Static Polarized Model to a Kinetic Model of Activation

Abstract: Our results show that the kinetic model of monocyte activation enables a dynamic approach for the evaluation of Q fever patients.

Cited by 29 publications

References 29 publications

Effect of Polarization and Chronic Inflammation on Macrophage Expression of Heparan Sulfate Proteoglycans and Biosynthesis Enzymes

Effect of Polarization and Chronic Inflammation on Macrophage Expression of Heparan Sulfate Proteoglycans and Biosynthesis Enzymes

Deconvolution of heterogeneous wound tissue samples into relative macrophage phenotype compositionviamodels based on gene expression

Murine Alveolar Macrophages Are Highly Susceptible to Replication of Coxiella burnetii Phase IIIn Vitro

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