Distinct monocyte subset phenotypes in patients with different clinical forms of chronic Chagas disease and seronegative dilated cardiomyopathy

Pérez‐Mazliah, Damián; Eiro, Melisa D. Castro; Alvarez, M; Lococo, Bruno; Bertocchi, Graciela; Cesar, Gonzalo; Natale, María A.; Albareda, María Cecilia; Viotti, Rodolfo; Laucella, Susana A.

doi:10.1371/journal.pntd.0006887

Cited by 9 publications

(7 citation statements)

References 41 publications

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“…In two previous works, in which the three monocyte subsets were identified in chronic chagasic patients, it also was found an increase of intermediate monocytes in cardiac patients (49, 50); although, we report different results regarding classical and non-classical monocytes percentages. These differences could be attributed to sample processing, staining reagents and distinct gating strategies for defining the subsets (52).…”

Section: Discussioncontrasting

confidence: 79%

“…Only few studies in Chagas disease have characterized the phenotype of the monocyte subsets based on CD14 and the CD16 expression, finding an increase of CD14+ CD16+ monocytes percentage in asymptomatic children (46, 47) and adults during acute and chronic infection (48–50). In this work, we studied the variations in the frequency of the total monocyte population, and the correlation between monocyte subsets and the seric levels of IL-1β, IL-1RA, IL-6, IL-10, IL-12p40, IL-12p70, IL-23, TNF-α, CCL17, and CXCL10 in samples from chronic chagasic patients with different stages of the disease.…”

Section: Introductionmentioning

confidence: 99%

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Intermediate Monocytes and Cytokine Production Associated With Severe Forms of Chagas Disease

et al. 2019

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Monocytes are classified according to their CD14 and CD16 expression into classical (reparative), intermediate (inflammatory), and non-classical. This study assessed the frequency of monocyte and the relationship between monocyte subset percentages and the levels of blood cytokines in Colombian chagasic patients with different clinical forms. This study included chagasic patients in different clinical stages: indeterminate (IND) n = 14, chronic chagasic cardiomyopathy (CCC) n = 14, and heart transplant chagasic (HTCC) n = 9; controls with non-chagasic cardiopathy (NCC) n = 15, and healthy individuals (HI) n = 15. Peripheral blood mononuclear cells (PBMCs) were isolated, labeled for CD14, CD16, and HLA-DR, and analyzed by flow cytometry. Cytokines were measured with a bead-based immunoassay. Percentages of total CD14+ CD16+ and CD14+ HLA-DR+ monocytes were higher in patients with heart involvement (CCC, HTCC, and NCC) than controls. Percentages of intermediate monocytes increased in symptomatic chagasic patients (CCC and HTCC) compared to asymptomatic chagasic patients (IND) and controls (HI). Asymptomatic chagasic patients (IND) had higher percentages of classical monocytes, an increased production of CCL17 chemokine compared to chagasic symptomatic patients (CCC), and their levels of CCL17 was positively correlated with the percentage of classical monocyte subset. In CCC, the percentages of intermediate and classical monocytes were positively correlated with IL-6 levels, which were higher in this group compared to HI, and negatively with IL-12p40 concentration, respectively. Remarkably, there also was an important increased of classical monocytes frequency in three chronic chagasic patients who underwent cardiac transplant, of which one received anti-parasitic treatment. Our findings suggest that cardiac chagasic patients have an increased percentage of inflammatory monocytes and produce more IL-6, a biomarker of heart failure and left ventricular dysfunction, whereas asymptomatic chagasic individuals present a higher percentage of reparative monocytes and CCL17.

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Section: Discussioncontrasting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Intermediate Monocytes and Cytokine Production Associated With Severe Forms of Chagas Disease

et al. 2019

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“…Regarding Chagas disease, our results are in full agreement with a recent report from Pérez-Mazliah's group. The authors found that T. cruzi-infected patients with mild or no signs of cardiac disease exhibited increased levels of nonclassical monocytes in comparison with control donors (38).…”

Section: Discussionmentioning

confidence: 98%

Monocyte glycolysis determines CD8+ T cell functionality in human Chagas disease

Sanmarco¹,

Eberhardt²,

Bergero³

et al. 2019

JCI Insight

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dinucleotide (NADH) and flavin adenine dinucleotide, which donate electrons to the electron transport chain to fuel oxidative phosphorylation (OXPHOS), the process by which 32 ATP molecules are generated in the mitochondria.In inflammatory settings, OXPHOS is inhibited by nitric oxide (NO) production in monocyte-derived inflammatory dendritic cells (moDCs) in an autocrine manner. In the absence of an active respiratory chain, sustained glycolytic metabolism is essential for moDC survival and function (9). Furthermore, NO production seems to be central in orchestrating HIF-1α responses by inducing its stabilization and transcriptional activation (10).Chagas disease, a complex pathological condition resulting from Trypanosoma cruzi infection, has become one of the most frequent causes of heart failure, cardio-embolic stroke, and sudden death in Latin America (11). The acute phase lasts 2-3 months and is characterized by detectable parasitemia and active parasite replication within target tissues. However, clinical symptoms are usually mild and nonspecific, and the vast majority of acute infections are never detected. During this phase, cell-mediated immunity controls parasite levels, but it is insufficient to completely clear the infection; most individuals remain infected for life. People who survive the acute phase enter a chronic asymptomatic phase (indeterminate stage), which is generally symptomless and may last from 10 to 30 years. Approximately 30% of patients in this period, also recognized as "silent," may develop heart abnormalities (12) that could give rise to the cardiac form of chronic infection. Although antiparasitic therapy is clearly recommended for acute Chagas disease, the treatment of patients in the chronic stage is controversial. This is largely due to a lack of large, randomized trials and incomplete understanding of pathological immune mechanisms developed during this stage. After decades of controversies, it is widely accepted nowadays that parasite persistence is a necessary and sufficient condition for the sustained inflammatory responses underlying the progression of cardiac lesions of chronic Chagas disease (13-18). Thus, one of the main challenges in understanding Chagas myocarditis immunopathology is to find out why, despite a robust immune response during the acute phase of the infection, the parasite is not completely eliminated, being able to sustain a pathological inflammatory environment.Cell-mediated immunity involves activation of phagocytes and of cytotoxic T lymphocytes (CTLs). In this sense, we have recently reported increased IL-1β plasma levels concomitant with enhanced frequency of NO-producing leukocytes and the surface nitration of CTLs associated with decreased functionality of this T cell compartment in the peripheral blood from patients with Chagas disease in the indeterminate phase (19). In this study, we went deeper by exploring how metabolism affects the monocyte compartment and T cell functionality during this human infectious disease. We have found that the nonc...

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“…As we have previously reported, during the first phase of sepsis there is a progressive polarization of monocytes to a pro-inflammatory phenotype characterized by the expansion of the CD14 ++ CD16 + subpopulation (intermediate monocytes, mainly a pro-inflammatory subset) and the decrease of classical CD14 ++ CD16monocytes subpopulation [22]. CD16 + monocytes are known to be involved in antigen processing and presen- [23], and to be increased during inflammation (e.g., cancer, sepsis and stroke), infections such as HIV, tuberculosis and other pathogens [24][25][26][27][28][29][30][31]. Other studies demonstrated intermediate monocytes involvement in inflammatory response by evidencing intermediate monocytes triggered expression of molecules, which promote their migration into the lesions, where increased levels of their ligand are present [32], also facilitated by increased permeability and endothelial activation [33].…”

Section: Discussionmentioning

confidence: 99%

Human Leukocyte Antigen-DR Isotype Expression in Monocytes and T Cells Interferon-Gamma Release Assay in Septic Patients and Correlation With Clinical Outcome

et al. 2021

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Background: Sepsis is a life-threatening dysregulated host response to infection responsible of multiple organs dysfunction (Sepsis-3 International Consensus Definition), during which clinical outcome is a balance between inflammation and immune suppression. Monocytes and lymphocytes may play an important role in immune paralysis, and their impaired functional activity can decrease overall immune system efficiency. We evaluated sepsis-induced changes in monocytes human leukocyte antigen-DR isotype (HLA-DR) expression and T cell capacity of interferon (IFN)-γ production in relation with patient's clinical outcome.Methods: Analysis of HLA-DR expression on blood monocytes (mH-LA-DR) was performed in 55 patients with high procalcitonin (hPCT, > 0.5 ng/mL,) and suspected/confirmed sepsis, and 20 controls. HLA-DR absolute quantification and IFN-γ release assay were monitored in 16 septic patients for 4 weeks following sepsis confirmation.Results: Cytofluorimetric analysis revealed a significant decrease of mHLA-DR percentage in septic patients with adverse outcome compared to patients with better clinical outcome (88.4% vs. 98.6% with P < 0.05), in combination with a significant decrease of absolute number of HLA-DR molecules per monocyte (P < 0.05, starting at 1 week of follow-up). Lymphocytes stimulation with phytohemagglutinin (PHA), Staphylococcus aureus (S. aureus) and Candida albicans (C. albicans) showed a severe declining of IFN-γ release related to fatal clinical outcome of patients. Conclusions:This immunologic anergy of innate and adaptative immunity showed an early immune paralysis during sepsis which appears correlated with the impairment of clinical outcome.

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Distinct monocyte subset phenotypes in patients with different clinical forms of chronic Chagas disease and seronegative dilated cardiomyopathy

Cited by 9 publications

References 41 publications

Intermediate Monocytes and Cytokine Production Associated With Severe Forms of Chagas Disease

Intermediate Monocytes and Cytokine Production Associated With Severe Forms of Chagas Disease

Monocyte glycolysis determines CD8+ T cell functionality in human Chagas disease

Human Leukocyte Antigen-DR Isotype Expression in Monocytes and T Cells Interferon-Gamma Release Assay in Septic Patients and Correlation With Clinical Outcome

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