Discovery of circulating miRNAs as biomarkers of chronic Chagas heart disease via a small RNA-Seq approach.

Chagas disease affects approximately 7 million people worldwide in Latin America and is a neglected tropical disease. Twenty to thirty percent of chronically infected patients develop chronic Chagas cardiomyopathy decades after acute infection. Identifying biomarkers of Chagas disease progression is necessary to develop better therapeutic and preventive strategies.

The long-term antibody response after SARS-CoV-2 prime-boost vaccination in healthy individuals. The positive influence of extended between-dose intervals and heterologous schedule.

Introduction: Anti-COVID vaccination in Argentina was carried out using different protocols and variations in periods between administrations, as well as combinations of different vaccine platforms. Considering the relevance of the antibody response in viral infections, we analyzed anti-S antibodies in healthy people at different points of time following the Sputnik immunization procedure.

Methods: We attended the vaccination centers in the city of Rosario, which had shorter versus longer intervals between both doses.

Enhanced Migratory Capacity of T Lymphocytes in Severe Chagasic Patients Is Correlated With VLA-4 and TNF-α Expression.

infection in humans leads to progression to chronic chagasic myocarditis (CCM) in 30% of infected individuals, paralleling T cell inflammatory infiltrates in the heart tissue. T-cell trafficking into the hearts of CCM patients may be modulated by expression of chemotactic or haptotactic molecules, as the chemokine CXCL12, the cytokine tumor necrosis factor-alpha (TNF-α), and extracellular matrix proteins (ECM), such as fibronectin. Herein we evaluated the expression of fibronectin, CXCL12, and TNF-α in the myocardial tissue of seropositive (asymptomatic or with CCM), as well as seronegative individuals as healthy controls.

Chagas disease reactivation in rheumatologic patients: association with immunosuppressive therapy and humoral response.

Evidence for Chagas disease reactivation (CDR) in rheumatologic patients under rheumatologic treatments (RTs) is scarce. To screen and follow-up patients with rheumatic diseases and concomitant Chagas disease under RT to detect CDR and to describe a possible relationship between CDR and specific RT. An observational, longitudinal, prospective, consecutive study was carried out between 2018 and 2020.

Evidence in Favor of an Alternative Glucocorticoid Synthesis Pathway During Acute Experimental Chagas Disease.

It is well-established that infectious stress activates the hypothalamus-pituitary-adrenal axis leading to the production of pituitary adrenocorticotropin (ACTH) and adrenal glucocorticoids (GCs). Usually, GC synthesis is mediated by protein kinase A (PKA) signaling pathway triggered by ACTH. We previously demonstrated that acute murine Chagas disease courses with a marked increase of GC, with some data suggesting that GC synthesis may be ACTH-dissociated in the late phase of this parasitic infection.

Immune-neuroendocrine and metabolic disorders in human and experimental T. cruzi infection: New clues for understanding Chagas disease pathology.

Studies in mice undergoing acute Trypanosoma cruzi infection and patients with Chagas disease, led to identify several immune-neuroendocrine disturbances and metabolic disorders. Here, we review relevant findings concerning such abnormalities and discuss their possible influence on disease physiopathology.

Immune response triggered by Trypanosoma cruzi infection strikes adipose tissue homeostasis altering lipid storage, enzyme profile and adipokine expression.

Adipose tissue is a target of Trypanosoma cruzi infection being a parasite reservoir during the chronic phase in mice and humans. Previously, we reported that acute Trypanosoma cruzi infection in mice is linked to a severe adipose tissue loss, probably triggered by inflammation, as well as by the parasite itself. Here, we evaluated how infection affects adipose tissue homeostasis, considering adipocyte anabolic and catabolic pathways, the immune-endocrine pattern and the possible repercussion upon adipogenesis.

Death of adrenocortical cells during murine acute T. cruzi infection is not associated with TNF-R1 signaling but mostly with the type II pathway of Fas-mediated apoptosis.

Earlier studies from our laboratory demonstrated that acute experimental Trypanosoma cruzi infection promotes an intense inflammation along with a sepsis-like dysregulated adrenal response characterized by normal levels of ACTH with raised glucocorticoid secretion. Inflammation was also known to result in adrenal cell apoptosis, which in turn may influence HPA axis uncoupling. To explore factors and pathways which may be involved in the apoptosis of adrenal cells, together with its impact on the functionality of the gland, we carried out a series of studies in mice lacking death receptors, such as TNF-R1 (C57BL/6- or TNF-R1) or Fas ligand (C57BL/6 Fas-deficient lpr mice), undergoing acute T.

miR-30c is specifically repressed in patients with active pulmonary tuberculosis.

Tuberculous pleurisy (PLTB) is a common form of extrapulmonary tuberculosis. It often resolves without chemotherapy being hence considered a rather benign manifestation of the disease. Patients with PLTB mount an effective anti-mycobacterial response, unlike those with active pulmonary TB (pTB) that were shown to present an imbalance in plasma immune and endocrine mediators.

Combined analysis of cross-reacting antibodies anti-β1AR and anti-B13 in advanced stages of Chagas heart disease.

Objective: Autoantibodies cross-reacting with the β1 adrenergic receptor (anti-β1AR and anti-p2β) and cardiac myosin antigens (anti-B13) have been related to the pathogenesis of chronic Chagas heart disease (CCHD). Studies exploring their levels in different stages are scarce. We aimed to evaluate the relationship of these autoantibodies with the clinical profile of chronic patients, especially regarding their classificatory accuracy in severe presentation with heart failure.

The Role of High Mobility Group Box 1 Protein (HMGB1) in the Immunopathology of Experimental Pulmonary Tuberculosis.

Background: The high mobility group box 1 (HMGB1) is the prototype of alarmin protein released by stressed or dying cells. The redox state of this protein confers different functions in the regulation of inflammation and immune response.

Aim: Determine the kinetics, cellular sources and function of HMGB1 in experimental tuberculosis.

Immunoendocrine interactions during HIV-TB coinfection: implications for the design of new adjuvant therapies.

Worldwide, around 14 million individuals are coinfected with both tuberculosis (TB) and human immunodeficiency virus (HIV). In coinfected individuals, both pathogens weaken immunological system synergistically through mechanisms that are not fully understood. During both HIV and TB infections, there is a chronic state of inflammation associated to dramatic changes in immune cytokine and endocrine hormone levels.

HIV-TB coinfection impairs CD8(+) T-cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses.

Tuberculosis (TB) is the leading cause of death among HIV-positive patients. The decreasing frequencies of terminal effector (TTE ) CD8(+) T cells may increase reactivation risk in persons latently infected with Mycobacterium tuberculosis (Mtb). We have previously shown that dehydroepiandrosterone (DHEA) increases the protective antitubercular immune responses in HIV-TB patients.

Immunoendocrine dysbalance during uncontrolled T. cruzi infection is associated with the acquisition of a Th-1-like phenotype by Foxp3(+) T cells.

We previously showed that Trypanosomacruzi infection in C57BL/6 mice results in a lethal infection linked to unbalanced pro- and anti-inflammatory mediators production. Here, we examined the dynamics of CD4(+)Foxp3(+) regulatory T (Treg) cells within this inflammatory and highly Th1-polarized environment. Treg cells showed a reduced proliferation rate and their frequency is progressively reduced along infection compared to effector T (Teff) cells.

Assessment of cross-reactive host-pathogen antibodies in patients with different stages of chronic Chagas disease.

Introduction And Objectives: Trypanosoma cruzi infection has been shown to induce humoral autoimmune responses against host antigens tissues. Particularly, antibodies cross-reacting with myocardial antigens may play a role in the development of the severe forms of chronic Chagas disease. The aim of this study was to determine the association between clinical stage of the disease and the presence of autoantibodies in patients with chronic Chagasic disease.

β1-selective adrenoceptor antagonists increase plasma levels of anti-p2β antibodies and decrease cardiac involvement in chronic progressive Chagas heart disease.

Background: Studies indicate that antibodies cross-reacting with cardiac β1 adrenergic receptors are likely to play a role in the development of chronic Chagas heart disease (CCHD). In parallel, clinical trials have shown that β1 antagonist drugs exert beneficial effects in the prognosis of patients with CCHD. In a group of patients with CCHD undergoing therapy with β1-blockers, we have now evaluated the levels of anti-p2β antibodies and the severity of CCHD.

Altered microRNA expression levels in mononuclear cells of patients with pulmonary and pleural tuberculosis and their relation with components of the immune response.

Different lines of evidence demonstrate that microRNAs (miRNAs) play an important role in host-pathogen interactions. In this study we investigated the expression patterns of several miRNAs, most of them involved in regulating inflammatory responses, in patients with tuberculosis (TB). In order to understand the events occurring at the site of infection, we employed mononuclear cells obtained from both peripheral blood (PBMC) and pleural fluids (PFMC) of patients.

Chronic Chagas disease with cardiodigestive involvement and the TcVI infective form of Trypanosoma cruzi. A case report.

We report a patient with megacolon associated with TcVI infective lineage form of Trypanosoma cruzi. Although this megacolon was considered idiopathic, Chagas disease was suspected and diagnosed because of the concomitant cardiovascular involvement. Based on this case, we discuss the suitability of Chagas diagnosis in patients with tract motility involvement.

Successful immunotherapy of canine flea allergy with injected Actinomycetales preparations.

Aims: Can heat-killed, borate-buffered suspensions of Gordonia bronchialis, Rhodococcus coprophilus or Tsukamurella inchonensis be used to treat canine flea allergy?

Materials & Methods: Organisms cultured on Sauton's medium into stationary phase were autoclaved in borate-buffered saline and stored at 10 mg wet weight/ml. Intradermal injections of 0.1 ml containing 1 mg of bacilli were administered on the first and 20th days of the study.

mRNA expression of alpha and beta isoforms of glucocorticoid receptor in peripheral blood mononuclear cells of patients with tuberculosis and its relation with components of the immunoendocrine response.

We have analyzed the expression of glucocorticoid receptor (GR) isoforms by real time RT-qPCR in PBMCs from 19 controls (HCo) and 28 TB patients (8 mild; 12 moderate; 8 severe), HIV(-) and similar sex and age distribution. mRNA hGRα/β ratios were found higher in TB patients respect to those in HCo. However, when analyzing for disease severity such overall trend was at the expense of mild and moderate patients, with severe cases showing a lower mRNA hGRα/β ratio with respect to the other patient groups.

Neuroendocrine-immunology of experimental Chagas' disease.

The cytokine-mediated stimulation of the hypothalamus-pituitary-adrenal (HPA) axis is relevant for immunoregulation and survival during bacterial endotoxemia and certain viral infections. However, only limited information is available regarding the effect of endogenous glucocorticoids on parasitic diseases. Here, we discuss evidence that the increased levels of corticosterone that occur following Trypanosoma cruzi infection in mice is an endocrine response that protects the host by impeding an excessive production of pro-inflammatory cytokines.