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BACKGROUND: OBJECTIVES: Evidence shows that CD4+ T cells are altered in obesity and play a significant role in the systemic inflammation in adults with the disease. Because the profile of these cells is poorly understood in the pediatric population, this study aims to investigate the profile of CD4+ T lymphocytes and the plasma levels of cytokines in this population. METHODS: Using flow cytometry, we compared the expression profile of lymphocyte markers, master transcription factors, cytokines, and molecules involved in the regulation of the immune response in CD4+ T cells from children and adolescents with obesity (OB group, n = 20) with those with eutrophy group (EU group, n = 16). Plasma levels of cytokines in both groups were determined by CBA. RESULTS: The OB group presents a lower frequency of CD3+ T cells, as well as a decreased frequency of CD4+ T cells expressing CD28, IL-4, and FOXP3, but an increased frequency of CD4+IL-17A+ cells compared with the EU group. The frequency of CD28 is increased in Th2 and Treg cells in the OB group, whereas CTLA-4 is decreased in all subpopulations compared with the EU group. Furthermore, Th2, Th17, and Treg profiles can differentiate the EU and OB groups. IL-10 plasma levels are reduced in the OB group and negatively correlated with adiposity and inflammatory parameters. CONCLUSIONS: CD4+ T cells have an altered pattern of expression in children and adolescents with obesity, contributing to the inflammatory state and clinical characteristics of these patients.

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CD4-CD8- (double negative - DN) T cells represent a small fraction of circulating T lymphocytes but are a major source of pro-inflammatory cytokines in patients with infectious diseases, including chronic Chagas cardiomyopathy (CCC), one of the deadliest cardiopathies known. Chagas disease is caused by an infection with the protozoan parasite Trypanosoma cruzi and can lead to either an asymptomatic form or a high-mortality cardiac disease. While circulating DN T cells represent a major inflammatory cytokine-expressing cell population in Chagas disease, their potential to be recruited to the heart and to perform cytotoxicity has not been determined. Our previous studies showed that blocking DN T cell activation decreases the expression of IFN-gamma, a cytokine involved in the severity of CCC. Here, studying a well-characterized cohort of Chagas patients with CCC or the asymptomatic form of Chagas disease (indeterminate form, IND), we evaluated the expression of cytotoxic molecules, cytokine and chemokine receptors in γδ+ and αß+ DN T cells by multiparameter flow cytometry, and investigated whether blocking the activation of DN T cells influences the expression of these molecules. We observed that DN T cells from CCC display a higher expression of granzyme A, perforin, inflammatory molecules, and inflammatory chemokine receptors than cells from IND. Messenger RNA coding for these molecules is also upregulated in the heart of CCC patients. Importantly, blocking the activation of DN T cells from CCC modulates their cytotoxic potential and the expression of inflammatory and of chemokine receptors, suggesting that targeting DN T cell activation may be a valid strategy to reduce recruitment to the heart, inflammation, cytotoxicity and, thereby diminish CCC progression and severity.

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In the 2 years since the COVID-19 pandemic was officially declared, science has made considerable strides in understanding the disease's pathophysiology, pharmacological treatments, immune response, and vaccination, but there is still much room for further advances, especially in comprehending its relationship with obesity. Science has not yet described the mechanisms that explain how obesity is directly associated with a poor prognosis. This paper gathers all published studies over the past 2 years that have described immune response, obesity, and COVID-19, a historical and chronological record for researchers and the general public alike. In summary, these studies describe how the cytokine/adipokine levels and inflammatory markers, such as the C-reactive protein, are associated with a higher body mass index in COVID-19-positive patients, suggesting that the inflammatory background and immune dysregulation in individuals with obesity may be expressed in the results and that adiposity may influence the immune response. The timeline presented here is a compilation of the results of 2 years of scientific inquiry, describing how the science has progressed, the principal findings, and the challenges ahead regarding SARS-CoV-2, COVID-19, and emerging variants, especially in patients with obesity.

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Chagas cardiomyopathy is the symptomatic cardiac clinical form (CARD) of the chronic phase of Chagas disease caused by Trypanosoma cruzi infection. It was described as the most fibrosing cardiomyopathies, affecting approximately 30% of patients during the chronic phase. Other less frequent symptomatic clinical forms have also been described. However, most patients who progress to the chronic form develop the indeterminate clinical form (IND), may remain asymptomatic for life, or develop some cardiac damage. Some mechanisms involved in the etiology of the clinical forms of Chagas disease have been investigated. To characterize the contribution of CD80 and CD86 co-stimulatory molecules in the activation of different CD4+ (Th1, Th2, Th17, and Treg) and CD8+ T lymphocyte subsets, we used blocking antibodies for CD80 and CD86 receptors of peripheral blood mononuclear cells (PBMC) in cultures with T. cruzi antigens from non-infected (NI), IND, and CARD individuals. We demonstrated a higher frequency of CD8+ CD25+ T lymphocytes and CD8+ Treg cells after anti-CD80 antibody blockade only in the CARD group. In contrast, a lower frequency of CD4+ Treg lymphocytes after anti-CD86 antibody blockade was found only in IND patients. A higher frequency of CD4+ Treg CD28+ lymphocytes, as well as an association between CD4+ Treg lymphocytes and CD28+ expression on CD4+ Treg cells in the CARD group, but not in IND patients, and once again only after anti-CD80 antibody blockade, was observed. We proposed that Treg cells from IND patients could be activated via CD86-CTLA-4 interaction, leading to modulation of the immune response only in asymptomatic patients with Chagas disease, while CD80 may be involved in the proliferation control of T CD8+ lymphocytes, as also in the modulation of regulatory cell activation via CD28 receptor. For the first time, our data highlight the role of CD80 in modulation of Treg lymphocytes activation in patients with CARD, highlighting a key molecule in the development of Chagas cardiomyopathy.

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Cytokines are involved in the immunopathogenesis of nonalcoholic fatty liver disease (NAFLD), but the relationship between them and clinical parameters of NAFLD progression is still unknown. Using flow cytometry, we evaluated the plasma levels of IL-1ß, IL-6, IL-12, TNF and IL-10 and their association with clinical and biochemical parameters of liver function during simple steatosis (NAFL) and nonalcoholic steatohepatitis (NASH) in biopsy-proven patients. The NASH patients showed higher levels of IL-6 associated with a lower IL-10/IL-6 ratio. Besides heatmaps were similar in the NAFL and NASH groups, the same did not occur in signature curves, the NASH patients were high producers to IL-12 and IL-6 while the NAFL patients were not high producers of any cytokines evaluated. Integrative biomarker network analysis revealed that cytokines are differently correlated with clinical parameters, while IL-12, IL-10 presented moderate and negative correlations with glycemic and lipid profile in the NAFL group. The NASH group IL-12 and TNF revealed stronger and positive correlations with transient elastography parameters and NAFLD liver fibrosis score. These data suggest that IL-6 and IL-10 might act in chronic inflammation and insulin resistance whereas IL-12 and TNF may be involved in promoting liver damage and NAFLD progression. Plasma concentration analysis of these molecules and their association with clinical parameters can be used as new biomarkers to monitoring NAFLD progression and to reflect NASH development.

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Childhood obesity is a global and increasing health issue. Inflammation and dysregulated adipose tissue secretion are common findings in obesity and have been related to poor metabolic function. Given that DNA methylation impacts gene expression and is responsive to environmental changes, we aimed, in addition to characterize the patients in anthropometric and biochemical terms, to determine the expression of cytokines and adipokines, assess the methylation on regulatory regions of the genes that code for these molecules, and investigate the association of the expression and gene methylation with anthropometric and biochemical parameters in childhood obesity. Obese children present dyslipidemia, dysregulated serum levels of adipokines and their ratios, altered leukocytic expression of cytokines, and higher methylation at the CXCL8 promoter as compared to the control group. However, no significant results were observed in the fasting plasma glucose levels or the methylation of TGFB1, LEP, and the enhancer region of ADIPOQ. We also found negative correlations of CXCL8 expression with anthropometric and biochemical parameters, and positive correlation of CXCL8 promoter methylation and the serum levels of hepatic enzymes. Our results indicate that changes in metabolic parameters observed in childhood obesity are associated with the expression of adipokines and cytokines, and the methylation status at the CXCL8 promoter. CXCL8 may be a key factor for these alterations, as it correlates with many of the parameters assessed in the present study.

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Leprosy, also known as Hansen's disease, is a long-term infection by the bacteria Mycobacterium leprae, and actually still persists as a serious public health problem. The clinical parameters are used for diagnosis, however, some studies have indicated the selection of a set of biomarkers of subclinical infection, both serological and cellular, that allow the early diagnosis. Some cytokines and chemokines have been differentially expressed in index cases (paucibacillary and multibacillary patients) and household contacts (HHC), and may present a potential biomarker of M. leprae subclinical infection. Thus, the aim of this study was to analyze the variations in the profile of cytokines and chemokines, longitudinally, between index cases and their household contacts with a view to identifying possible biomarkers with differential expression, which may guide the early subclinical infection in household contacts. A longitudinal study was carried out between 2014 and 2015. The serum levels of the cytokines and chemokines were measured in all patient samples by CBA (Cytometric Bead Array). We observed a reduction of IL-4 and IL-17 expression of HHC group in the second evaluation (T1), as also a reduction of IL-17 in MB. We observed increased expression of IL-2 in PB patients as well. HHC, PB and MB showed a similar reduction profile of the chemokines CXCL8, CXCL9 and CXCL10 from T0 to T1. Interestingly, only serological levels of CCL2 are increased after a follow-up of HHC group, and this group, but not PB and MB patients, showed a significant association and a negative correlation between CCL2 and IFN-γ. The present study showed for the first time a similarity in the immunological scenario between HHC, PB and MB patients. In addition, this work highlights CCL2 chemokine in association with IFN-γ as possible biomarkers of subclinical infection of HHC, as also a parameter of early infection monitoring.

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In 2002/2003 there was a pandemic denominate SARS (severe acute respiratory syndrome), caused by the SARS-CoV virus that belongs to the genera Betacoranavirus and the family Coronaviridae, generally responsible for influenza infections. In mid of 2019, a new disease by the coronavirus named by COVID-19 (SARS-CoV-2) emerged, both infections have flu symptoms, however they are infections that variable intensity, being medium to severe. In medium infections individuals have the virus and exhibit symptoms, however hospitalization is not necessary, in severe infections, individuals are hospitalized, have high pathology and in some cases progress to death. The virus is formed by simple positive RNA, enveloped, non-segmented, and presenting the largest genome of viruses constituting 32 Kb, consisting of envelope proteins, membrane, nucleocapsid and spike protein, which is essential in the interaction with the host cells. As for the origin of this virus, research has been intensified to determine this paradox and although the similarity with SARS-CoV, this virus did not has necessarily the same place of origin. As for the immune system, it is currently unknown how this new virus interacts. In this brief review, we demonstrate important considerations about the responses to this infection.

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One of the major challenges in chronic Chagas disease is to understand the mechanisms that predict the clinical evolution from asymptomatic to severe cardiac clinical forms. Our cohort consisted of twenty-eight Chagas disease patients followed for twenty years. Plasma levels of MMP-2 and MMP-9 gelatinases and TIMPs were evaluated by multiplexed immunoassay at two points in time with an average interval of six years. MMP-2 plasma levels, but not MMP-9, increased in cardiac patients over time. TIMP-1 levels diminished in cardiac patients, while TIMP-3 dropped in asymptomatic patients in the course of the evaluated interval. An inversion of time lines was observed relative to the clinical asymptomatic and cardiac forms for MMP-2. Receiver Operating Characteristic (ROC) curve analysis identified MMP-2 as a biomarker to distinguish asymptomatic from cardiac clinical forms, while MMP-9 is a biomarker that segregates infected from non-infected patients. We have pointed out that MMP-2 and MMP-9 together can predict clinical evolution in Chagas disease. MMP-2 was suggested as a biomarker for fibrosis replacement in early remodeling and a sensitive predictor for initial changes in asymptomatic patients that may evolve into the cardiac clinical form. MMP-9 seems to be a biomarker for late fibrosis and severe cardiac remodeling in cardiac patients.

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