Juliana Reis Machado

Mucosal Immunity in the Female Genital Tract, HIV/AIDS

Mucosal immunity consists of innate and adaptive immune responses which can be influenced by systemic immunity. Despite having been the subject of intensive studies, it is not fully elucidated what exactly occurs after HIV contact with the female genital tract mucosa. The sexual route is the main route of HIV transmission, with an increased risk of infection in women compared to men. Several characteristics of the female genital tract make it suitable for inoculation, establishment of infection, and systemic spread of the virus, which causes local changes that may favor the development of infections by other pathogens, often called sexually transmitted diseases (STDs). The relationship of these STDs with HIV infection has been widely studied. Here we review the characteristics of mucosal immunity of the female genital tract, its alterations due to HIV/AIDS, and the characteristics of coinfections between HIV/AIDS and the most prevalent STDs.

Neonatal Sepsis and Inflammatory Mediators

Neonatal sepsis is a major cause of morbidity and mortality and its signs and symptoms are nonspecific, which makes the diagnosis difficult. The routinely used laboratory tests are not effective methods of analysis, as they are extremely nonspecific and often cause inappropriate use of antibiotics. Sepsis is the result of an infection associated with a systemic inflammatory response with production and release of a wide range of inflammatory mediators. Cytokines are potent inflammatory mediators and their serum levels are increased during infections, so changes from other inflammatory effector molecules may occur. Although proinflammatory and anti-inflammatory cytokines have been identified as probable markers of neonatal infection, in order to characterize the inflammatory response during sepsis, it is necessary to analyze a panel of cytokines and not only the measurement of individual cytokines. Measurements of inflammatory mediators bring new options for diagnosing and following up neonatal sepsis, thus enabling early treatment and, as a result, increased neonatal survival. By taking into account the magnitude of neonatal sepsis, the aim of this review is to address the role of cytokines in the pathogenesis of neonatal sepsis and its value as a diagnostic criterion.

Complexity and Controversies over the Cytokine Profiles of T Helper Cell Subpopulations in Tuberculosis

Tuberculosis (TB) is a contagious infectious disease caused by the TB-causing bacillus Mycobacterium tuberculosis and is considered a public health problem with enormous social impact. Disease progression is determined mainly by the balance between the microorganism and the host defense systems. Although the immune system controls the infection, this control does not necessarily lead to sterilization. Over recent decades, the patterns of CD4+ T cell responses have been studied with a goal of complete understanding of the immunological mechanisms involved in the maintenance of latent or active tuberculosis infection and of the clinical cure after treatment. Conflicting results have been suggested over the years, particularly in studies comparing experimental models and human disease. In recent years, in addition to Th1, Th2, and Th17 profiles, new standards of cellular immune responses, such as Th9, Th22, and IFN-γ-IL-10 double-producing Th cells, discussed here, have also been described. Additionally, many new roles and cellular sources have been described for IL-10, demonstrating a critical role for this cytokine as regulatory, rather than merely pathogenic cytokine, involved in the establishment of chronic latent infection, in the clinical cure after treatment and in keeping antibacillary effector mechanisms active to prevent immune-mediated damage.

An Overview of Molecular Mechanism of Nephrotic Syndrome

Podocytopathies (minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS)) together with membranous nephropathy are the main causes of nephrotic syndrome. Some changes on the expression of nephrin, podocin, TGF-β, and slit diaphragm components as well as transcription factors and transmembrane proteins have been demonstrated in podocytopathies. Considering the pathogenesis of proteinuria, some elucidations have been directed towards the involvement of epithelial-mesenchymal transition. Moreover, the usefulness of some markers such as TGF-β1, nephrin, synaptopodin, dystroglycans, and malondialdehyde have been determined in the differentiation between MCD and FSGS. Experimental models and human samples indicated an essential role of autoantibodies in membranous glomerulonephritis, kidney damage, and proteinuria events. Megalin and phospholipase-A2-receptor have been described as antigens responsible for the formation of the subepithelial immune complexes and renal disease occurrence. In addition, the complement system seems to play a key role in basal membrane damage and in the development of proteinuria in membranous nephropathy. This paper focuses on the common molecular changes involved in the development of nephrotic proteinuria.

T Cell Activation and Proinflammatory Cytokine Production in Clinically Cured Tuberculosis Are Time-Dependent and Accompanied by Upregulation of IL-10.

Background Th1 cytokines are essential for the control of M. tuberculosis infection. The role of IL-10 in tuberculosis is controversial and there is an increasing body of evidence suggesting that the relationship between Th1 cytokines and IL-10 is not as antagonistic as it was first believed, and that these cytokines may complement each other in infectious diseases. Methods The present study evaluated the activating capacity of CD4+ and CD8+ T cell repertoire in response to antigen stimulation through the expression of CD69 using Flow Cytometry, as well as the functionality of PBMCs by determining the cytokine profile in patients with active tuberculosis and in clinically cured patients after in vitro stimulation using ELISA. Treated patients were subdivided according to time after clinical cure (<12 months or >12 months post-treatment). Results We observed that T cell activation was higher in TB-treated patients, especially CD8+ T cell activation in TB-Treated >1 year. Th1 cytokines were significantly higher in TB-Treated, and the levels of IFN-γ and TNF-α increased continuously after clinical cure. Moreover, IL-10 production was significantly higher in cured patients and it was also enhanced in cured patients over time after treatment. Th17, Th2 and Th22 cytokines showed no statistically significant differences between Healthy Donors, Active-TB and TB-Treated. Conclusions This study describes a scenario in which potentiation of CD4+ and CD8+ T cell activation and increased Th1 cytokine production are associated with the clinical cure of tuberculosis in the absence of significant changes in Th2 cytokine production and is accompanied by increased production of IL-10. In contrast to other infections with intracellular microorganisms, this response occurs later after the end of treatment.

Intrauterine infection, immune system and premature birth

Abstract Preterm birth accounts for nearly one million deaths among children under five years of age, and although its etiopathogenesis is not fully elucidated, ascending intrauterine infection and fetal inflammatory response seem to be the main triggers. The intense inflammatory response mediated by IL-1β, TNF-α, PAF, IFN-γ and IL-6, PGE2 and MMP-1 and MMP-9 causes fetal membrane damage and rupture, increased uterine contractions and biochemical and structural changes in the cervix. Furthermore, preterm neonates have deficient innate and adaptive immune responses characterized by reduced levels of IgG, opsonization and phagocytosis, as well as increased activation of Th1 cells in relation to Th2 cells. Therefore, this triad is favors the occurrence of neonatal complications, such as respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity and bronchopulmonary dysplasia. Due to serious maternal and child health complications of intrauterine infection, several studies have tried to identify biomarkers for the early diagnosis of this entity. This literature review aims to discuss the main scientific findings regarding the association between ascending intrauterine infection, immune system and preterm birth.

Pulmonary innate immune response and melatonin receptors in the perinatal stress.

Objective. To analyze the cytokines of the innate immune pulmonary response and the capacity for local response to melatonin according to the perinatal stress. Methods. 49 cases of pediatric autopsies were evaluated, divided according to cause of death, perinatal stress, gestational age, and birth weight. The percentages of IL-6, C-reactive protein (CRP), IL-1β, TNF-α, and melatonin receptor were evaluated by immunohistochemistry. Results. The IL-6 expression was higher in the children showing chronic stress, anoxia, and infection. The IL-6 expression showed a progressive increase according to the relation between weight and GA. There was no significant difference in the expression of IL-1β and TNF-α. The CRP expression was higher in the cases showing chronic stress and premature cases. The expression of melatonin receptors was significantly higher in the cases showing chronic stress, being more evident in the cases showing infection. Conclusion. The cause of death and the type of stress influence the expression in situ of melatonin and cytokines of the innate immune pulmonary response. The evaluation of IL-6 and CRP may contribute to the understanding of the evolution of neonates with chronic stress. The greater sensitivity of the lung to melatonin in these cases may indicate an attempt at controlling the immunological response, in an attempt to diminish the harmful effects of stress.

Assessment of oxidative status markers and NO bioavailability in hypertensive disorders of pregnancy

The systemic oxidative status in hypertensives disorders of pregnancy (HDP) and its association with endothelial dysfunction is controversial. In the present study, we evaluated systemic plasma levels of oxidative stress markers (TBARS (thiobarbituric acid-reactive substances) and carbonyl) and total antioxidant status (FRAP (ferric reducing ability of plasma (ferric reducing/antioxidant power) and reduction of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide))), as well as assessed the impact these markers have on nitric oxide (NO) status in healthy pregnant (HP, n=38), gestational hypertensive (GH, n=33) and preeclamptic pregnant women (PE, n=28). We found similar values of TBARS among all groups, and reduced carbonyl levels in HDP between the PE and GH. Conversely, significant increases in plasma activity of antioxidant status were observed in the GH and PE groups compared to the HP group (using both MTT or FRAP method). Importantly, HDP present significantly lower nitrite levels compared to HP women. In Conclusion, our findings show a compensatory antioxidant mechanism against reactive oxygen species (ROS) generation in HDP, which is not associated with nitrite levels restoration.

Fetal wound healing biomarkers.

Fetal skin has the intrinsic capacity for wound healing, which is not correlated with the intrauterine environment. This intrinsic ability requires biochemical signals, which start at the cellular level and lead to secretion of transforming factors and expression of receptors, and specific markers that promote wound healing without scar formation. The mechanisms and molecular pathways of wound healing still need to be elucidated to achieve a complete understanding of this remodeling system. The aim of this paper is to discuss the main biomarkers involved in fetal skin wound healing as well as their respective mechanisms of action.

Expression Pattern of Transcription Factors and Intracellular Cytokines Reveals That Clinically Cured Tuberculosis Is Accompanied by an Increase in Mycobacterium-Specific Th1, Th2, and Th17 Cells

Tuberculosis (TB) remains a major global health problem and is the second biggest cause of death by infectious disease worldwide. Here, we investigate in vitro the Th1, Th2, Th17, and Treg cytokines and transcriptional factors produced after Mycobacterium-specific antigen stimulation in patients with active pulmonary tuberculosis, clinically cured pulmonary tuberculosis, and healthy donors with a positive tuberculin skin test (TST+). Together, our data indicate that clinical cure after treatment increases the percentages of Mycobacterium-specific Th1, Th2, and Th17 cells compared with those found in active-TB and TST+ healthy donors. These results show that the host-parasite equilibrium in latent TB breaks in favor of the microorganism and that the subsequent clinical recovery posttreatment does not return the percentage levels of such cells to those observed in latent tuberculosis. Additionally, our results indicate that rather than showing an increase in the percentage of Mycobacterium-specific Tregs, active-TB patients display lower Th1 : Treg and Th17 : Treg ratios. These data, together with lower Th1 : Th2 and Th17 : Th2 ratios, may indicate a mechanism by which the breakdown of the host-parasite equilibrium leads to active-TB and changes in the repertoire of Mycobacterium-specific Th cells that are associated with clinical cure after treatment of pulmonary tuberculosis.