Role of the Aryl Hydrocarbon Receptor in the Immune Response Profile and Development of Pathology during Plasmodium berghei Anka Infection

Brant, Fátima; Miranda, Aline Silva de; Esper, Lísia; Rodrigues, David Henrique; Kangussu, Lucas M.; Bonaventura, Daniella; Soriani, Frederico Marianetti; Pinho, Vanessa; Souza, Danielle G.; Weiss, Louis M.; Tanowitz, Herbert B.; Teixeira, Antônio Lúcio; Machado, Fabiana S.

doi:10.1128/iai.01733-14

Cited by 28 publications

(36 citation statements)

References 75 publications

(114 reference statements)

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“…A recent study revealed that SOCS3 acts as an inhibitor of the JAK/ STAT5a pathway and disturbs lipogenesis by decreasing Srebp-1c expression (43). Also, AhR modulated the basal expression of Socs3 in spleen and brain (44). These results suggest that the lipotoxicities observed following HFD feeding in AhR LKO mice were attributed to a lower level of Socs3 expression.…”

Section: Discussionmentioning

confidence: 44%

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Aryl Hydrocarbon Receptor Plays Protective Roles against High Fat Diet (HFD)-induced Hepatic Steatosis and the Subsequent Lipotoxicity via Direct Transcriptional Regulation of Socs3 Gene Expression

Wada

Sunaga

Miyata

et al. 2016

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 44%

“…9, A-F). A recent study reported by Brant et al (44) showed that AhR is involved in a SOCS3-mediated immune response. Consequently, we are led to conclude that AhR plays protective roles against HFDinduced hepatic steatosis and the subsequent lipotoxicity via direct transcriptional regulation of Socs3 expression in the liver.…”

Section: Discussionmentioning

confidence: 99%

Aryl Hydrocarbon Receptor Plays Protective Roles against High Fat Diet (HFD)-induced Hepatic Steatosis and the Subsequent Lipotoxicity via Direct Transcriptional Regulation of Socs3 Gene Expression

Wada

Sunaga

Miyata

et al. 2016

Journal of Biological Chemistry

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“…IL-12 and IFN-␥ are important cytokines released during innate and acquired immune responses to control T. cruzi infection (13). Several reports have suggested that AhR is part of a regulatory pathway that inhibits the proinflammatory response in several models of infection (8,9,11). In order to ascertain whether this was the case in T. cruzi infection, we used flow cytometry to evaluate the production of these cytokines by different immune cell populations in the spleen at 10 dpi.…”

Section: Deficiency Of Ahr Results In a Reduction Of In Vitro Ros Promentioning

confidence: 99%

“…Splenic cells from infected and control mice were evaluated ex vivo for the expression of extracellular molecules, intracellu-lar cytokines, and ROS at 10 dpi. Cell suspensions were prepared as previously described (9). Each sample comprised individual mice splenic cell suspensions that were stained with specific combinations of antibodies:…”

Section: Methodsmentioning

confidence: 99%

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The Aryl Hydrocarbon Receptor Modulates Production of Cytokines and Reactive Oxygen Species and Development of Myocarditis during Trypanosoma cruzi Infection

et al. 2016

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eThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in controlling several aspects of immune responses, including the activation and differentiation of specific T cell subsets and antigen-presenting cells, thought to be relevant in the context of experimental Trypanosoma cruzi infection. The relevance of AhR for the outcome of T. cruzi infection is not known and was investigated here. We infected wild-type (WT) mice and AhR knockout (AhR KO) mice with T. cruzi (Y strain) and determined levels of parasitemia, myocardial inflammation and fibrosis, expression of AhR/cytokines/suppressor of cytokine signaling (SOCS) (spleen/heart), and production of nitric oxide (NO), reactive oxygen species (ROS), and peroxynitrite (ONOO ؊ ) (spleen). AhR expression was increased in the heart of infected WT mice. Infected AhR KO mice displayed significantly reduced parasitemia, inflammation, and fibrosis of the myocardium. This was associated with an anticipated increased immune response characterized by increased levels of inflammatory cytokines and reduced expression of SOCS2 and SOCS3 in the heart. In vitro, AhR deficiency caused impairment in parasite replication and decreased levels of ROS production. In conclusion, AhR influences the development of murine Chagas disease by modulating ROS production and regulating the expression of key physiological regulators of inflammation, SOCS1 to -3, associated with the production of cytokines during experimental T. cruzi infection. The aryl hydrocarbon receptor (AhR) was originally described as a ligand-dependent transcription factor for exogenous ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) capable of activating the aryl hydrocarbon hydroxylase (1, 2). In humans and mice, AhR recognizes several endogenous ligands, such as 6-formylindolo[3,2-b]carbazole (FICZ), kynurenines, indoles (3, 4), and lipoxins (LX) (5). The activation of the AhR signaling pathway controls the genomic expression of diverse target genes, leading to different physiological outcomes (6). More recently, it has been recognized that AhR is involved in the regulation of several immune processes. The major immune mechanisms controlled by AhR are related to the activation and differentiation of specific T cell subsets (T regulatory [Treg] and Th17) and antigenpresenting cells (3). In the context of immunity to infections, it was demonstrated that AhR is an essential protein for murine resistance to Listeria monocytogenes (7) and toxoplasmosis (8).More recently, we found that it was an important factor in controlling parasitemia and inflammation during experimental cerebral malaria (9). Additionally, it is associated with antiviral immunity (10) and is a negative regulator of inflammatory cytokines in response to Leishmania major experimental infection (11). Taken together, the results of these studies strongly suggest that AhR function during immune responses to infections is complex and likely pathogen specific.Trypanosoma cruzi is a flagellated protozoan parasite that...

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Genetic analysis of cerebral malaria in the mouse model infected with Plasmodium berghei

Langlais

Gros

2018

Mamm Genome

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Malaria is a common and sometimes fatal disease caused by infection with Plasmodium parasites. Cerebral malaria (CM) is a most severe complication of infection with Plasmodium falciparum parasites which features a complex immunopathology that includes a prominent neuroinflammation. The experimental mouse model of cerebral malaria (ECM) induced by infection with Plasmodium berghei ANKA has been used abundantly to study the role of single genes, proteins and pathways in the pathogenesis of CM, including a possible contribution to neuroinflammation. In this review, we discuss the Plasmodium berghei ANKA infection model to study human CM, and we provide a summary of all host genetic effects (mapped loci, single genes) whose role in CM pathogenesis has been assessed in this model. Taken together, the reviewed studies document the many aspects of the immune system that are required for pathological inflammation in ECM, but also identify novel avenues for potential therapeutic intervention in CM and in diseases which feature neuroinflammation.

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Role of the Aryl Hydrocarbon Receptor in the Immune Response Profile and Development of Pathology during Plasmodium berghei Anka Infection

Cited by 28 publications

References 75 publications

Aryl Hydrocarbon Receptor Plays Protective Roles against High Fat Diet (HFD)-induced Hepatic Steatosis and the Subsequent Lipotoxicity via Direct Transcriptional Regulation of Socs3 Gene Expression

Aryl Hydrocarbon Receptor Plays Protective Roles against High Fat Diet (HFD)-induced Hepatic Steatosis and the Subsequent Lipotoxicity via Direct Transcriptional Regulation of Socs3 Gene Expression

The Aryl Hydrocarbon Receptor Modulates Production of Cytokines and Reactive Oxygen Species and Development of Myocarditis during Trypanosoma cruzi Infection

Genetic analysis of cerebral malaria in the mouse model infected with Plasmodium berghei

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