Interaction Between Macrophages and Cryptococcus neoformans: Distinguishing Phagocytosed Versus External Fungi.

The interaction between macrophages and Cryptococcus neoformans is crucial in the pathogenesis of cryptococcosis. These phagocytes are important immune effectors, but also a niche in which facultative intracellular parasites, such as C. neoformans, thrive. Consequently, phagocytosis of cryptococcal cells and its outcomes are very frequently studied. One major issue with several of the tests used for this, however, is that macrophage-C. neoformans interaction does not always result in phagocytosis, as fungi may be attached to the external surface of the phagocyte. The most used methodologies to study phagocytosis of cryptococcal cells have varying degrees of precision in separating fungi that are truly internalized from those that are outside macrophages. Here we describe two assays to measure phagocytosis that can differentiate internal from external C. neoformans cells.

Metacyclogenesis as the Starting Point of Chagas Disease.

Chagas disease is a neglected infectious disease caused by the protozoan Trypanosoma cruzi, primarily transmitted by triatomine vectors, and it threatens approximately seventy-five million people worldwide. This parasite undergoes a complex life cycle, transitioning between hosts and shifting from extracellular to intracellular stages. To ensure its survival in these diverse environments, T. cruzi undergoes extreme morphological and molecular changes. The metacyclic trypomastigote (MT) form, which arises from the metacyclogenesis (MTG) process in the triatomine hindgut, serves as a crucial link between the insect and human hosts and can be considered the starting point of Chagas disease. This review provides an overview of the current knowledge regarding the parasite's life cycle, molecular pathways, and mechanisms involved in metabolic and morphological adaptations during MTG, enabling the MT to evade the immune system and successfully infect human cells.

The First Contact of Human Dendritic Cells With Trypanosoma cruzi Reveals Response to Virus as an Unexplored Central Pathway.

Chagas disease is a debilitating and neglected disease caused by the protozoan Trypanosoma cruzi. Soon after infection, interactions among T. cruzi and host innate immunity cells can drive/contribute to disease outcome. Dendritic cells (DCs), present in all tissues, are one of the first immune cells to interact with Trypanosoma cruzi metacyclic trypomastigotes. Elucidating the immunological events triggered immediately after parasite-human DCs encounter may aid in understanding the role of DCs in the establishment of infection and in the course of the disease. Therefore, we performed a transcriptomic analysis of a 12 h interaction between T. cruzi and MoDCs (monocyte-derived DCs) from three human donors. Enrichment analyses of the 468 differentially expressed genes (DEGs) revealed viral infection response as the most regulated pathway. Additionally, exogenous antigen processing and presentation through MHC-I, chemokine signaling, lymphocyte co-stimulation, metallothioneins, and inflammasome activation were found up-regulated. Notable, we were able to identify the increased gene expression of alternative inflammasome sensors such as AIM2, IFI16, and RIG-I for the first time in a T. cruzi infection. Both transcript and protein expression levels suggest proinflammatory cytokine production during early T. cruzi-DCs contact. Our transcriptome data unveil antiviral pathways as an unexplored process during T. cruzi-DC initial interaction, disclosing a new panorama for the study of Chagas disease outcomes.

Prolyl Oligopeptidase From Leishmania infantum: Biochemical Characterization and Involvement in Macrophage Infection.

Leishmania infantum is a flagellated protozoan and one of the main causative agents of visceral leishmaniasis. This disease usually affects the human reticuloendothelial system, can cause death and available therapies may lead to serious side effects. Since it is a neglected tropical disease, the incentives for the development of new drugs are insufficient. It is important to know Leishmania virulence factors that contribute most to the disease in order to develop drugs. In the present work, we have produced L. infantum prolyl oligopeptidase (rPOPLi) in Escherichia coli, and investigated its biochemical properties as well as the effect of POP inhibitors on its enzymatic activity and on the inhibition of the macrophage infection by L. infantum. The optimal activity occurred at pH 7.5 and 37°C in the presence of DTT, the latter increased rPOPLi catalytic efficiency 5-fold on the substrate N-Suc-Gly-Pro-Leu-Gly-Pro-AMC. The enzyme was inhibited by TPCK, TLCK and by two POP specific inhibitors, Z-Pro-prolinal (ZPP, IC50 4.2 nM) and S17092 (IC50 3.5 nM). Besides being a cytoplasmic enzyme, POPLi is also found in punctuate structures within the parasite cytoplasm or associated with the parasite plasma membrane in amastigotes and promastigotes, respectively. Interestingly, S17092 and ZPP prevented parasite invasion in murine macrophages, supporting the involvement of POPLi in the invasive process of L. infantum. These data suggest POPLi as a virulence factor that offers potential as a target for designing new antileishmanial drugs.

Atuação da fisioterapia na reabilitação de paciente com Síndrome de Guillain-Barré / Physical therapy performance in rehabilitation of patient with Guillain-Barré Syndrome

Introdução: A Síndrome de Guillain-Barré (SBG) é definida como uma polirradiculoneuropatia inflamatória aguda, autoimune, em que ocorre a desmielinização dos nervos periféricos, causando fraqueza motora e alterações sensoriais. A evolução da SGB é caracterizada pela progressiva perda motora, que em geral afeta primeiro os membros inferiores progredindo para os superiores, e pela hiporreflexia ou arreflexia, com comprometimento do nervo craniano. A fase aguda pode durar algumas semanas, engloba o início dos sintomas e a estabilização da desmielinização. Após esse período inicia-se a fase de recuperação, que coincide com a remielinização e regeneração dos axônios. Objetivo: O presente estudo tem como objetivo avaliar a eficácia da fisioterapia no processo de reabilitação de pacientes portadores da SGB, observando abordagens diversas e principalmente ressaltar a importância da atenção fisioterapêutica durante esse processo. Métodos: Foi realizada uma revisão da literatura dos últimos 10 anos que abordassem o tema da SGB associada à Fisioterapia. Resultados: Em todos os casos estudados, embora cada um com sua particularidade em relação à necessidade da reabilitação, foram observadas melhoras significativas, com ganho de capacidade funcional fundamental para independência em atividades diárias. Conclusão: Foi possível concluir que a intervenção fisioterapêutica é muito importante e eficaz na recuperação das limitações funcionais ocasionadas pela SGB, promovendo ao portador independência nas atividades diárias e melhorando a qualidade de vida. (AU)

Guillain-Barré Syndrome (GBS) is defined as an acute, autoimmune, inflammatory polyradiculoneuropathy in which peripheral nerves demyelination occurs, causing motor weakness and sensory changes. The evolution of GBS is characterized by progressive motor loss, which generally affects first the lower limbs progressing to the superiors, and by hyporeflexia or arreflexia, with impairment of the cranial nerves. The acute phase may last for a few weeks, encompasses the onset of symptoms and the stabilization of demyelination. After this period begins the recovery phase, which coincides with the demyelization and regeneration of the axons. Objective: The objective of this study was to evaluate the effectiveness of physical therapy in the rehabilitation process of patients with GBS, observing different approaches and especially emphasizing the importance of physical therapeutic attention during this process. Method: Literature review of the last 10 years on GBS associated to Physical therapy. Results: In all the cases studied, although each with its particularity in relation to need for rehabilitation, significant improvements were observed, with gain of functional capacity. Conclusion: We conclude that the physical therapy intervention is effective in the recovery of the functional limitations caused by GBS, promoting the independence in daily activities and improving the quality of life. (AU)