IL-12 and IL-27 regulate the phagolysosomal pathway in mycobacteria-infected human macrophages

Jung, Joo-Yong; Robinson, Cory M.

doi:10.1186/1478-811x-12-16

Cited by 46 publications

(89 citation statements)

References 40 publications

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“…63,64 IL-27 also confers immunosuppressive properties to several immune cells. Although the anti-inflammatory role of IL-27 has been reported during the course of inflammation, 52,65 knowledge is limited about its role during the regulation of myeloid cell polarization and in the regulation of innate immunity. IHC analysis of ovarian cancer tissues revealed that tumor-infiltrating neutrophils represent the main source of IL-27.…”

Section: Discussionmentioning

confidence: 99%

The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27

et al. 2016

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(2016) The ectoATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSFmacrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27, OncoImmunology, 5:7, e1178025, DOI: 10.1080/2162402X.2016 Targeting mediators that control the generation or the differentiation of immunoregulatory macrophages represents a therapeutic challenge to overcome tumor-associated immunosuppression. The ectonucleotidase CD39 hydrolyzes ATP into extracellular adenosine that exhibits potent immunosuppressive properties when signaling through the A2A adenosine receptor. We report here that CD14 C CD163 C TAM isolated from ovarian cancer patients and macrophages generated in vitro with M-CSF, express high levels of the membrane ectonucleotidase CD39 compared to classically activated macrophages. The CD39 inhibitor POM-1 and adenosine deaminase (ADA) diminished some of the immunosuppressive functions of CD14 high CD163 high CD39 high macrophages, such as IL-10 secretion. We identified the cytokine IL-27, secreted by tumor-infiltrating neutrophils, located close to infiltrating CD163 C macrophages, as a major rheostat of CD39 expression and consequently, on the acquisition of immunoregulatory properties by macrophages. Accordingly, the depletion of IL-27 downregulated CD39 and PD-L1 expression as well as IL-10 secretion by M-CSF-macrophages. Collectively, these data suggest that CD39, drived by IL-27 and CD115 ligands in ovarian cancer, maintains the immunosuppressive phenotype of TAM. This work brings new information on the acquisition of immunosuppressive properties by tumor-infiltrating macrophages.

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Section: Discussionmentioning

confidence: 99%

The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27

et al. 2016

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“…12 It is believed 16,[39][40] Previous studies also emphasized on the role of IL-27 in bacterial infections. 41 Jung and associates showed the role of IL-27 and also STAT-3 on lysosomal activity, which finally renders to enhanced trafficking of mycobacteria toward lysosomes in human macrophages. 41 The role of IL-27 in the pathogenesis of other viral infections show its prominent role in removing viruses, for example; study of the role of IL-27 in influenza virus type A replication and gene expression showed inhibition and antiviral function of IL-27 which enforced by activation of STAT1/2/3.…”

Section: Discussionmentioning

confidence: 99%

“…41 Jung and associates showed the role of IL-27 and also STAT-3 on lysosomal activity, which finally renders to enhanced trafficking of mycobacteria toward lysosomes in human macrophages. 41 The role of IL-27 in the pathogenesis of other viral infections show its prominent role in removing viruses, for example; study of the role of IL-27 in influenza virus type A replication and gene expression showed inhibition and antiviral function of IL-27 which enforced by activation of STAT1/2/3. 42 Wang and associates carried out a gene expression profiling study and found that IL-27 serum levels were significantly higher in HBV-infected patients in comparing with healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Untitled

Zare

Karimi²,

Rashki³

et al. 2017

Exp Clin Transplant

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Objectives: Hepatitis B viral infection is among the most common causes of cirrhosis and hepatocellular carcinoma and a frequent viral indication for liver transplant. Cytokine-mediated immunity plays a critical role in introducing and promoting hepatitis B virus outcomes and in graft microenvironment. Interleukin 27 is a heterodimeric cytokine and a member of interleukin-6/interleukin-12 family. Interleukin-27 shows a broad range of pro-and antiinflammatory properties and plays a determining role during immune responses in combating hepatitis B virus. Therefore, in this study, the possible association between expressions of interleukin-27 gene with hepatitis B virus infection was evaluated in liver transplant patients. Materials and Methods: In a cross-sectional study from liver transplant patients with the risk of hepatitis B virus infection who admitted to Namazi Hospital affiliated to Shiraz University of Medical Sciences, 50 patients were selected and subgrouped to 25 hepatitis B virus-infected and 25 noninfected ones between years 2011 and 2013. The 25 healthy controls also were enrolled in this study. The presence of hepatitis B virus infection was assessed using polymerase chain reaction and enzyme-linked immunosorbent assay protocols in liver transplant patients. In addition, the interleukin-27 gene expression level was analyzed using an in-house-SYBER Green real time polymerase chain reaction method. The rate of interleukin-27 gene expression level was statistically analyzed in studied patient groups and controls using the Livak (2-ΔΔCT ) method. Results:The expression level of interleukin-27 gene was increased 10.27-and 2.36-fold in hepatitis B virusinfected and uninfected liver transplanted patients compared with healthy controls. Conclusion: Hepatitis B virus infection can lead to overexpression of interleukin-27 gene in liver transplant patients compared with uninfected ones and controls. However, further studies are needed to characterize the effective antihepatitis B virus effects of interleukin-27 in liver transplant patients.

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“…This alkaline pH hinders the transport of material from early endosomes to late endosomes arresting the phagosome maturation [29]. In human macrophages Jung and Robinson [30] have shown that infected macrophages express the P28 and the Epstein-Barr virus induced gene s (EBI3) proteins and the cell secretes the active IL-27. The IL-27 then engages its receptor on the same cell and down regulates the expression of the v-ATPase.…”

Section: Mechanisms Used By Mycobacteria To Evade Immune System and Smentioning

confidence: 99%

Macrophage Infection by Mycobacteria

Saleh¹

2016

Mycobact Dis

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Mycobacterium tuberculosis is the etiological agent of tuberculosis. It is a pathogen that continues to draw international concerns particularly due to the emergence of multi-drug resistance and to the difficulties associated with the diagnosis and treatment of latent tuberculosis. A key process in the pathogenesis of this disease is the interaction between this pathogen and host macrophages. Invasion of the macrophages protects the pathogen from attack by the immune system, allows it to multiply while protected within the macrophages, and alters the immune response as it influences the profiles of the cytokine and chemokine responses. Key to the intracellular survival of the pathogen within the macrophages is the specific interaction between the pathogen and its virulence factors with the host. This review provides an a summary of pertinent literature on the topic of macrophage receptors utilized by the pathogen, its survival strategies within the macrophage, and the general profile of immune signalling upon exposure to the pathogen. The importance of specific macrophage receptors and certain components of the pathogen to the direction of the immune response are also discussed.

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IL-12 and IL-27 regulate the phagolysosomal pathway in mycobacteria-infected human macrophages

Cited by 46 publications

References 40 publications

The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27

The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27

Untitled

Macrophage Infection by Mycobacteria

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