Genes associated with alternatively activated macrophages discretely regulate helminth infection and pathogenesis in experimental mouse models

Horsnell, William G. C.; Brombacher, Frank

doi:10.1016/j.imbio.2010.05.011

Cited by 18 publications

(11 citation statements)

References 49 publications

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“…Since co-expression of CD14 and CD56 can occur, monocytes were defined as CD3 − CD56 − CD14 + cells [37]. Helminthic infections are known to result in a Th2-dominated immune response and S. mansoni induce alternatively activated macrophages that contribute to different functions, such as fibrosis, depending on the stage of the infection [38]–[40].…”

Section: Discussionmentioning

confidence: 99%

Effect of Female Genital Schistosomiasis and Anti-Schistosomal Treatment on Monocytes, CD4+ T-Cells and CCR5 Expression in the Female Genital Tract

Kleppa

Ramsuran

Zulu³

et al. 2014

PLoS ONE

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Background Schistosoma haematobium is a waterborne parasite that may cause female genital schistosomiasis (FGS), characterized by genital mucosal lesions. There is clinical and epidemiological evidence for a relationship between FGS and HIV. We investigated the impact of FGS on HIV target cell density and expression of the HIV co-receptor CCR5 in blood and cervical cytobrush samples. Furthermore we evaluated the effect of anti-schistosomal treatment on these cell populations.DesignThe study followed a case-control design with post treatment follow-up, nested in an on-going field study on FGS.MethodsBlood and cervical cytobrush samples were collected from FGS negative and positive women for flow cytometry analyses. Urine samples were investigated for schistosome ova by microscopy and polymerase chain reaction (PCR).ResultsFGS was associated with a higher frequency of CD14+ cells (monocytes) in blood (11.5% in FGS+ vs. 2.2% in FGS-, p = 0.042). Frequencies of CD4+ cells expressing CCR5 were higher in blood samples from FGS+ than from FGS- women (4.7% vs. 1.5%, p = 0.018). The CD14+ cell population decreased significantly in both compartments after anti-schistosomal treatment (p = 0.043). Although the frequency of CD4+ cells did not change after treatment, frequencies of CCR5 expression by CD4+ cells decreased significantly in both compartments (from 3.4% to 0.5% in blood, p = 0.036; and from 42.4% to 5.6% in genital samples, p = 0.025).ConclusionsThe results support the hypothesis that FGS may increase the risk of HIV acquisition, not only through damage of the mucosal epithelial barrier, but also by affecting HIV target cell populations, and that anti-schistosomal treatment can modify this.

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Section: Discussionmentioning

confidence: 99%

Effect of Female Genital Schistosomiasis and Anti-Schistosomal Treatment on Monocytes, CD4+ T-Cells and CCR5 Expression in the Female Genital Tract

Kleppa

Ramsuran

Zulu³

et al. 2014

PLoS ONE

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“…In this study, we examined IL-4+IL-13-induced or M2a macrophages (hereafter referred to as AAMs), which in mice are characterized by increased expression of arginase 1 (Arg1), Ym1 (a chitinase-like molecule) and RELMα (resistin-like molecule α). In humans, other markers, such as PPARγ and CD206 can be used for identification of AAMs [5].…”

Section: Introductionmentioning

confidence: 99%

The Pro-Inflammatory Cytokine, Interleukin-6, Enhances the Polarization of Alternatively Activated Macrophages

et al. 2014

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Macrophages are important innate immune cells that are associated with two distinct phenotypes: a pro-inflammatory (or classically activated) subset with prototypic macrophage functions such as inflammatory cytokine production and bactericidal activity, and an anti-inflammatory (or alternatively activated (AAM)) subset linked with wound healing and tissue repair processes. In this study, we examined the effect of interlukein-6 on human and murine macrophage polarization. The results indicate that despite being commonly associated with pro-inflammatory functions and being implicated in the pathogenesis/pathophysiology of numerous inflammatory diseases, interleukin-6 can enhance the polarization of AAMs, based on increased expression of hallmark markers: arginase-1, Ym1 and CD206; this effect required the AAM differentiating cytokines, IL-4 and IL-13. Co-treatment of AAMs with IL-6 resulted in spontaneous release of IL-10, suppressed LPS-induced nitric oxide production and inhibited cytokine production by activated CD4+ T cells – immunoregulatory features not observed in the ‘parent’ IL-4+IL-13-induced AAM. The effect of IL-6 required signal transducer and activator of transcription (STAT)-3, was partially dependent on up-regulation of the IL4Rα chain, and was independent of autocrine IL-10. In the presence of IFNγ, IL-6 promoted the production of IL-1β and TNFα suggesting that this cytokine can enhance the phenotype to which a macrophage has committed. This finding may explain the pleiotrophic nature of IL-6, where it is associated with the perpetuation and enhancement of disease in inflammatory situations, but is also necessary for resolution of inflammation and adequate wound healing to occur in others. Thus, the potential benefit of IL-6 in promoting an AAM, with its’ anti-inflammatory and wound healing ability, may need to be considered in immunotherapies aimed at in vivo modulation or inhibition of IL-6.

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“…Open Access these factors are arginase 1, chemokine (C-C motif) ligand 13 (CCL13), platelet-derived growth factor (PDGF), mannose receptor 1 (mrc-1) and, in murine macrophages, found in inflammatory zone 1 (fizz1), for instance [4,[8][9][10]. Likewise, also in clinical settings, alternatively activated macrophages have been linked to defence against extracellular pathogens, and to resolution of inflammation, wound healing and fibrosis [11][12][13].…”

Section: Research Articlementioning

confidence: 99%

Peroxisome proliferator-activated receptor α and γ agonists differently regulate classical and alternative macrophage activation

Paukkeri¹,

Pekurinen²,

Moilanen³

2015

Immunometabolism

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Genes associated with alternatively activated macrophages discretely regulate helminth infection and pathogenesis in experimental mouse models

Cited by 18 publications

References 49 publications

Effect of Female Genital Schistosomiasis and Anti-Schistosomal Treatment on Monocytes, CD4+ T-Cells and CCR5 Expression in the Female Genital Tract

Effect of Female Genital Schistosomiasis and Anti-Schistosomal Treatment on Monocytes, CD4+ T-Cells and CCR5 Expression in the Female Genital Tract

The Pro-Inflammatory Cytokine, Interleukin-6, Enhances the Polarization of Alternatively Activated Macrophages

Peroxisome proliferator-activated receptor α and γ agonists differently regulate classical and alternative macrophage activation

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