Role of formyl peptide receptor 2 (FPR2) in modulating immune response and heart inflammation in an experimental model of acute and chronic Chagas disease

Pereira, Rafaela das Dores; Rabelo, Rayane Aparecida Nonato; Leite, Paulo Gaio; Cramer, Allysson; Botelho, Ana Flávia Machado; Cruz, Jáder Santos; Régis, Wiliam César Bento; Perretti, Mauro; Teixeira, Mauro Martins; Machado, Fabiana S.

doi:10.1016/j.cellimm.2021.104427

Cited by 8 publications

(4 citation statements)

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“…Although there was no difference between the characteristics of parasitemia observed in the two mice groups in the present study, other study reported significantly lower parasitemia in the same FPR2-/- mice, than that observed in WT mice [ 30 ]. The latter results are consistent with other experimental models, wherein the deletion of the gene encoding 5-lipoxygenase (5-LO), which participates in the biosynthesis of lipoxins, also showed reduced parasitemia [ 25 , 30 ]. However, in other studies, 5-LO deficiency led to increased parasitemia without affecting survival or infection control [ 31 , 32 ].…”

Section: Discussioncontrasting

confidence: 79%

“…In the experimental model used, the course of parasitemia in the WT and FPR2 -/mice was representative of the behavior expected by the Dm28c strain of T. cruzi [19,29]. Although there was no difference between the characteristics of parasitemia observed in the two mice groups in the present study, other study reported significantly lower parasitemia in the same FPR2-/mice, than that observed in WT mice [30]. The latter results are consistent with other experimental models, wherein the deletion of the gene encoding 5-lipoxygenase (5-LO), which…”

Section: Involvement Of Inflammation Resolution In Parasitemia Controlsupporting

confidence: 57%

“…participates in the biosynthesis of lipoxins, also showed reduced parasitemia [25,30]. However, in other studies, 5-LO deficiency led to increased parasitemia without affecting survival or infection control [31,32].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 93%

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Aspirin-triggered resolvin D1 reduces parasitic cardiac load by decreasing inflammation in a murine model of early chronic Chagas disease

et al. 2021

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Background Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and is widely distributed worldwide because of migration. In 30% of cases, after years of infection and in the absence of treatment, the disease progresses from an acute asymptomatic phase to a chronic inflammatory cardiomyopathy, leading to heart failure and death. An inadequate balance in the inflammatory response is involved in the progression of chronic Chagas cardiomyopathy. Current therapeutic strategies cannot prevent or reverse the heart damage caused by the parasite. Aspirin-triggered resolvin D1 (AT-RvD1) is a pro-resolving mediator of inflammation that acts through N-formyl peptide receptor 2 (FPR2). AT-RvD1 participates in the modification of cytokine production, inhibition of leukocyte recruitment and efferocytosis, macrophage switching to a nonphlogistic phenotype, and the promotion of healing, thus restoring organ function. In the present study, AT-RvD1 is proposed as a potential therapeutic agent to regulate the pro-inflammatory state during the early chronic phase of Chagas disease. Methodology/Principal findings C57BL/6 wild-type and FPR2 knock-out mice chronically infected with T. cruzi were treated for 20 days with 5 μg/kg/day AT-RvD1, 30 mg/kg/day benznidazole, or the combination of 5 μg/kg/day AT-RvD1 and 5 mg/kg/day benznidazole. At the end of treatment, changes in immune response, cardiac tissue damage, and parasite load were evaluated. The administration of AT-RvD1 in the early chronic phase of T. cruzi infection regulated the inflammatory response both at the systemic level and in the cardiac tissue, and it reduced cellular infiltrates, cardiomyocyte hypertrophy, fibrosis, and the parasite load in the heart tissue. Conclusions/Significance AT-RvD1 was shown to be an attractive therapeutic due to its regulatory effect on the inflammatory response at the cardiac level and its ability to reduce the parasite load during early chronic T. cruzi infection, thereby preventing the chronic cardiac damage induced by the parasite.

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Section: Discussioncontrasting

confidence: 79%

Section: Involvement Of Inflammation Resolution In Parasitemia Controlsupporting

confidence: 57%

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Aspirin-triggered resolvin D1 reduces parasitic cardiac load by decreasing inflammation in a murine model of early chronic Chagas disease

et al. 2021

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“…AnxA1 is expressed in a variety of immune cells such as neutrophils, monocytes, macrophages, and mast cells [ 24 , 25 , 26 ]. Then, by acting on the Formyl-peptide receptor 2 ( FPR2 )/ ALXR , AnxA1 is responsible for regulating neutrophil migration to inflammatory sites, inducing neutrophil apoptosis and decreasing inflammation and pain in different experimental models [ 27 , 28 , 29 , 30 , 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection

Araújo

Costa

Santos

et al. 2022

Cells

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Chikungunya (CHIKV) is an arthritogenic alphavirus that causes a self-limiting disease usually accompanied by joint pain and/or polyarthralgia with disabling characteristics. Immune responses developed during the acute phase of CHIKV infection determine the rate of disease progression and resolution. Annexin A1 (AnxA1) is involved in both initiating inflammation and preventing over-response, being essential for a balanced end of inflammation. In this study, we investigated the role of the AnxA1-FPR2/ALX pathway during CHIKV infection. Genetic deletion of AnxA1 or its receptor enhanced inflammatory responses driven by CHIKV. These knockout mice showed increased neutrophil accumulation and augmented tissue damage at the site of infection compared with control mice. Conversely, treatment of wild-type animals with the AnxA1 mimetic peptide (Ac2–26) reduced neutrophil accumulation, decreased local concentration of inflammatory mediators and diminished mechanical hypernociception and paw edema induced by CHIKV-infection. Alterations in viral load were mild both in genetic deletion or with treatment. Combined, our data suggest that the AnxA1-FPR2/ALX pathway is a potential therapeutic strategy to control CHIKV-induced acute inflammation and polyarthralgia.

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Role of Suppressor of cytokine signaling 2 during the development and resolution of an experimental arthritis

Cramer

Galvão

Sá

et al. 2022

Cellular Immunology

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Role of formyl peptide receptor 2 (FPR2) in modulating immune response and heart inflammation in an experimental model of acute and chronic Chagas disease

Cited by 8 publications

References 50 publications

Aspirin-triggered resolvin D1 reduces parasitic cardiac load by decreasing inflammation in a murine model of early chronic Chagas disease

Aspirin-triggered resolvin D1 reduces parasitic cardiac load by decreasing inflammation in a murine model of early chronic Chagas disease

Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection

Role of Suppressor of cytokine signaling 2 during the development and resolution of an experimental arthritis

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