Interaction of Signaling Lymphocytic Activation Molecule Family 1 (SLAMF1) receptor with Trypanosoma cruzi is strain-dependent and affects NADPH oxidase expression and activity

Poveda, Cristina; Herreros-Cabello, Alfonso; Callejas-Hernández, Francisco; Osuna-Pérez, Jesús; Maza, María del Carmen Lapo; Chillón-Marinas, Carlos; Calderón, Jossela; Stamatakis, Konstantinos; Fresno, Manuel; Gironès, Núria

doi:10.1371/journal.pntd.0008608

Cited by 7 publications

(6 citation statements)

References 35 publications

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“…Histological data, in concordance with the previous report from our group [27], showed a moderate auricular inflammatory reaction with Y strain infection (Figure 5). Although no evidence of the infection is shown here, parasite load was quantified in the same cardiac samples in a previously published manuscript [28], indicating cardiac parasitization. The right atrial cell population was evaluated on this occasion with more detail, suggesting nodal-like cell depopulation.…”

Section: Discussionmentioning

confidence: 47%

Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis

et al. 2021

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Chagas disease principally affects Latin-American people, but it currently has worldwide distribution due to migration. Death among those with Chagas disease can occur suddenly and without warning, even in those who may not have evidence of clinical or structural cardiac disease and who are younger than 60 years old. HCN4 channels, one of the principal elements responsible for pacemaker currents, are associated with cardiac fetal reprogramming and supraventricular and ventricular arrhythmias, but their role in chagasic arrhythmias is not clear. We found that a single-dose administration of ivabradine, which blocks HCN4, caused QTc and QRS enlargement and an increase in P-wave amplitude and was associated with ventricular and supraventricular arrhythmias in mice challenged with isoproterenol, a chronotropic/ionotropic positive agent. Continuous treatment with ivabradine did not alter the QTc interval, but P-wave morphology was deeply modified, generating supraventricular arrhythmias. In addition, we found that repolarization parameters improved with ivabradine treatment. These effects could have been caused by the high HCN4 expression observed in auricular and ventricular tissue in infected mice. Thus, we suggest, for the first time, that molecular remodeling by overexpression of HCN4 channels may be related to supraventricular arrhythmias in acute Chagas disease, causing ivabradine over-response. Thus, ivabradine treatment should be administered with caution, while HCN4 overexpression may be an indicator of heart failure and/or sudden death risk.

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Section: Discussionmentioning

confidence: 47%

Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis

et al. 2021

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“…Moreover, Slamf1-defIcient myeloid cells are impaired in their ability to replicate the parasite, and they display an altered pattern of cytokine production. Recent studies by Poveda et al [ 27 ] have shown that the interaction of SLAMF1 with T. cruzi is strain-dependent and affects NOX2 expression and ROS production, since five out of six strains tested showed a decrease in parasite load in Slamf1 −/− infected macrophages compared to wild-type macrophages. Also, NOX2 expression and ROS production were increased in Slamf1 −/− infected macrophages when compared to wild-type macrophages [ 27 ].…”

Section: Inflammation and Oxidative Damage In Chagas Diseasementioning

confidence: 99%

The Oxidative Stress and Chronic Inflammatory Process in Chagas Disease: Role of Exosomes and Contributing Genetic Factors

Maldonado

Rojas

Urbina

et al. 2021

Oxidative Medicine and Cellular Longevity

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Chagas disease is a neglected tropical disease caused by the flagellated protozoa Trypanosoma cruzi that affects several million people mainly in Latin American countries. Chagas disease has two phases, which are acute and chronic, both separated by an indeterminate time period in which the infected individual is relatively asymptomatic. The acute phase extends for 40-60 days with atypical and mild symptoms; however, about 30% of the infected patients will develop a symptomatic chronic phase, which is characterized by either cardiac, digestive, neurological, or endocrine problems. Cardiomyopathy is the most important and severe result of Chagas disease, which leads to left ventricular systolic dysfunction, heart failure, and sudden cardiac death. Most deaths are due to heart failure (70%) and sudden death (30%) resulting from cardiomyopathy. During the chronic phase, T. cruzi-infected macrophages respond with the production of proinflammatory cytokines and production of superoxide and nitric oxide by the NADPH oxidase 2 (NOX2) and inducible nitric oxide synthase (iNOS) enzymes, respectively. During the chronic phase, myocardial changes are produced as a result of chronic inflammation, oxidative stress, fibrosis, and cell death. The cellular inflammatory response is mainly the result of activation of the NF-κB-dependent pathway, which activates gene expression of inflammatory cytokines, leading to progressive tissue damage. The persisting production of reactive oxygen species (ROS) is the result of mitochondrial dysfunction in the cardiomyocytes. In this review, we will discuss inflammation and oxidative damage which is produced in the heart during the chronic phase of Chagas disease and recent evidence on the role of macrophages and the production of proinflammatory cytokines during the acute phase and the origin of macrophages/monocytes during the chronic phase of Chagas disease. We will also discuss the contributing factors and mechanisms leading to the chronic inflammation of the cardiac tissue during the chronic phase of the disease as well as the innate and adaptive host immune response. The contribution of genetic factors to the progression of the chronic inflammatory cardiomyopathy of chronic Chagas disease is also discussed. The secreted extracellular vesicles (exosomes) produced for both T. cruzi and infected host cells can play key roles in the host immune response, and those roles are described. Lastly, we describe potential treatments to attenuate the chronic inflammation of the cardiac tissue, designed to improve heart function in chagasic patients.

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“…In addition, Slamf1 -/macrophages became more resistant to the infection with the same strain. More recently, we described increased resistance of Slamf1 -/macrophages to the infection with other parasite strains (Dm28c, M6421, 10R26, and Bug2148) except for one (VFRA) (Poveda et al, 2020). This correlated with the increased expression of NOX-2 expression and ROS production in Slamf1 -/macrophages infected with all the strains except VFRA in comparison to the WT.…”

Section: Role Of Slamf1 Receptor On Ros Generation and Mdsc Expansion During Trypanosoma Cruzi Infectionmentioning

confidence: 66%

“…These opposing strain-dependent roles of SLAMF1 in infectivity and ROS production may explain some of the mentioned discrepancies in the chapter above about the role of ROS in T. cruzi infection. Moreover, Slamf1 -/mice infected with the Y strain showed a shift from MDSC expansion to M1 polarization compared to the WT (Poveda et al, 2020), suggesting that SLAMF1 may have a role in emergency myelopoiesis and possibly mediating MDSCs expansion, a possibility that should be explored in the future.…”

Section: Role Of Slamf1 Receptor On Ros Generation and Mdsc Expansion During Trypanosoma Cruzi Infectionmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells in Trypanosoma cruzi Infection

Fresno

Gironès

2021

Front. Cell. Infect. Microbiol.

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Myeloid-derived suppressor cells (MDSCs) are immature heterogeneous myeloid cells that expand in pathologic conditions as cancer, trauma, and infection. Although characterization of MDSCs is continuously revisited, the best feature is their suppressor activity. There are many markers for MDSC identification, it is distinctive that they express inducible nitric oxide synthase (iNOS) and arginase 1, which can mediate immune suppression. MDSCs can have a medullary origin as a result of emergency myelopoiesis, but also can have an extramedullary origin. Early studies on Trypanosoma cruzi infection showed severe immunosuppression, and several mechanisms involving parasite antigens and host cell mediators were described as inhibition of IL-2 and IL-2R. Another mechanism of immunosuppression involving tumor necrosis factor/interferon γ-dependent nitric oxide production by inducible nitric oxide synthase was also described. Moreover, other studies showed that nitric oxide was produced by CD11b+ Gr-1+ MDSCs in the spleen, and later iNOS and arginase 1 expressed in CD11b+Ly6C+Ly6Glo monocytic MDSC were found in spleen and heart of T. cruzi infected mice that suppressed T cell proliferation. Uncontrolled expansion of monocytic MDSCs leads to L-arginine depletion which hinders nitric oxide production leading to death. Supplement of L-arginine partially reverts L-arginine depletion and survival, suggesting that L-arginine could be administered along with anti-parasitical drugs. On the other hand, pharmacological inhibition of MDSCs leads to death in mice, suggesting that some expansion of MDSCs is needed for an efficient immune response. The role of signaling molecules mediating immune suppression as reactive oxygen species, reactive nitrogen species, as well as prostaglandin E2, characteristics of MDSCs, in T. cruzi infection is not fully understood. We review and discuss the role of these reactive species mediators produced by MDSCs. Finally, we discuss the latest results that link the SLAMF1 immune receptor with reactive oxygen species. Interaction of the parasite with the SLAMF1 modulates parasite virulence through myeloid cell infectivity and reactive oxygen species production. We discuss the possible strategies for targeting MDSCs and SLAMF1 receptor in acute Trypanosoma cruzi infection in mice, to evaluate a possible translational application in human acute infections.

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Interaction of Signaling Lymphocytic Activation Molecule Family 1 (SLAMF1) receptor with Trypanosoma cruzi is strain-dependent and affects NADPH oxidase expression and activity

Cited by 7 publications

References 35 publications

Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis

Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis

The Oxidative Stress and Chronic Inflammatory Process in Chagas Disease: Role of Exosomes and Contributing Genetic Factors

Myeloid-Derived Suppressor Cells in Trypanosoma cruzi Infection

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