RESUMO
Many pathogenic organisms need to reach either an intracellular compartment or the cytoplasm of a target cell for their survival, replication or immune system evasion. Intracellular pathogens frequently penetrate into the cell through the endocytic and phagocytic pathways (clathrin-mediated endocytosis, phagocytosis and macropinocytosis) that culminates in fusion with lysosomes. However, several mechanisms are triggered by pathogenic microorganisms - protozoan, bacteria, virus and fungus - to avoid destruction by lysosome fusion, such as rupture of the phagosome and thereby release into the cytoplasm, avoidance of autophagy, delaying in both phagolysosome biogenesis and phagosomal maturation and survival/replication inside the phagolysosome. Here we reviewed the main data dealing with phagosome maturation and evasion from lysosomal killing by different bacteria, protozoa, fungi and virus.
Assuntos
Lisossomos , Fagocitose , Lisossomos/microbiologia , Fagossomos/metabolismo , Fagossomos/microbiologia , Endocitose , Evasão da Resposta ImuneRESUMO
ABSTRACT: Bertolaccini, AL, da Silva, AA, Teixeira, EL, Schoenfeld, BJ, and de Salles Painelli, V. Does the expectancy on the static stretching effect interfere with strength-endurance performance? J Strength Cond Res 35(9): 2439-2443, 2021-Static stretching (SS) may interfere with strength performance. Such interference, however, may be partially attributed to the subjects' or researcher's expectancy about the SS effects. We aimed to examine whether the manipulation of subjects' expectancy of SS on force production could influence strength-endurance during unilateral knee extension exercise. Eighteen strength-trained men were randomly divided into positively biased (PB; N = 9) or negatively biased (N = 9) groups on the possible effects of SS on performance. Subjects' total number of repetitions and total volume of exercise were assessed during strength-endurance tests (4 sets performed to failure at 70% of 1 repetition maximum) performed under 2 different conditions on separate days: Control-no stretching (CON); or SS. Static stretching consisted of 3 sets of 3 stretching exercises, lasting 30 seconds each. Data were analyzed using mixed models. Neither the total number of repetitions nor the total volume was significantly different between the CON and SS conditions, nor for type of bias (all p > 0.05). However, the number of repetitions in the last set of exercise was greater during SS compared with CON for the PB group (p = 0.01). Although previous negative or positive information about SS did not interfere with the total number of repetitions and total volume of exercise, previous positive information about SS improved performance in the last set of exercise. Expectancy therefore may have played a partial role influencing strength-endurance in previous studies.
Assuntos
Exercícios de Alongamento Muscular , Humanos , Masculino , Músculo Esquelético , Estado Nutricional , Resistência FísicaRESUMO
Trypanosoma cruzi P21 protein (P21) is a putative secreted and immunomodulatory molecule with potent bioactive properties such as induction of phagocytosis and actin cytoskeleton polymerization. Despite the bioactive properties described so far, the action of P21 on parasite replication in muscle cell lineage or T. cruzi parasitism during acute experimental infection is unclear. We observed that recombinant P21 (rP21) decreased the multiplication of T. cruzi in C2C12 myoblasts, phenomenon associated with greater actin polymerization and IFN-γ and IL-4 higher expression. During experimental infection, lower cardiac nests, inflammatory infiltrate and fibrosis were observed in mice infected and treated with rP21. These results were correlated with large expression of IFN-γ counterbalanced by high levels of IL-10, which was consistent with the lower cardiac tissue injury found in these mice. We have also observed that upon stress, such as that induced by the presence of the IFN-γ cytokine, T. cruzi produced more P21. The effect of P21 in controlling the replication of T. cruzi, may indicate an evolutionary mechanism of survival developed by the parasite. Thus, when subjected to different stress conditions, the protozoan produces more P21, which induces T. cruzi latency in the host organism, enabling the protozoan to evade the host's immune system.
Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Malária/parasitologia , Mioblastos/parasitologia , Miocárdio/patologia , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/fisiologia , Doença Aguda , Animais , Linhagem Celular , Interações Hospedeiro-Parasita , Humanos , Evasão da Resposta Imune , Peptídeos e Proteínas de Sinalização Intercelular/genética , Interferon gama/metabolismo , Malária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Carga Parasitária , Proteínas de Protozoários/genéticaRESUMO
B cells contribute to the immune system in many ways such as antigen presentation to CD4+ T cells, secretion of cytokines and lymphoid tissue organogenesis. Furthermore, they are the only cell type capable of producing immunoglobulins. B cells also account for critical aspects of the resistance against intracellular pathogens. Trypanosoma cruzi is an intracellular parasite that sabotages humoral response by depletion of immature B cells. Polyclonal activation and secretion of non-specific antibodies are also other mechanisms used by T cruzi to evade and subvert the mammalian host immune system, leading to increased parasitemia and susceptibility to Chagas' disease. It remained unclear whether B cell depletion occurs due to direct contact with T. cruzi or results from a global increase in inflammation. Unlike previous reports, we demonstrated in this study that T. cruzi infects human B cells, resulting in parasite-induced activation of caspase-7 followed by proteolytic cleavage of phospholipase Cγ1 and cell death. These data contribute to explain the mechanisms ruling B-cell depletion and evasion of the immune response by T. cruzi.
Assuntos
Actinas/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Caspase 7/metabolismo , Interações Hospedeiro-Patógeno , Fosfolipase C gama/metabolismo , Trypanosoma cruzi/imunologia , Morte Celular , Doença de Chagas/imunologia , Doença de Chagas/metabolismo , Doença de Chagas/parasitologia , Humanos , ProteóliseRESUMO
IL-9 is a pleiotropic cytokine, recently recognized as belonging to Th9 cells that are involved in various pathologies. We aimed to evaluate the role of IL-9 in the course of hepatic and renal fibrosis. Female C57BL/6 mice were treated subcutaneously with IL-9 10 ng/mouse and 20 ng/mouse for 40 days, alternating every 5 days each application, the negative control of which was treated with PBS and positive control with CCL4. IL-9 demonstrated fibrogenic activity, leading to increased collagen I and III deposition in both liver and kidney, as well as triggering lobular hepatitis. In addition, IL-9 induced an inflammatory response with recruitment of lymphocytes, neutrophils, and macrophages to both organs. The inflammation was present in the region of the portal and parenchymal zone in the liver and in the cortical and medullary zone in the kidney. IL-9 deregulated liver and kidney antioxidant activities. Our results showed that IL-9 was able to promote hepatorenal dysfunction. Moreover, IL-9 poses as a promising target for therapeutic interventions.
Assuntos
Fibrose/etiologia , Interleucina-9/efeitos adversos , Rim/patologia , Fígado/patologia , Animais , Colágeno/metabolismo , Feminino , Inflamação/induzido quimicamente , Inflamação/patologia , Rim/fisiologia , Fígado/fisiologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Chronic chagasic cardiomyopathy (CCC) is arguably the most important form of the Chagas Disease, caused by the intracellular protozoan Trypanosoma cruzi; it is estimated that 10-30% of chronic patients develop this clinical manifestation. The most common and severe form of CCC can be related to ventricular abnormalities, such as heart failure, arrhythmias, heart blocks, thromboembolic events and sudden death. Therefore, in this study, we proposed to evaluate the anti-angiogenic activity of a recombinant protein from T. cruzi named P21 (rP21) and the potential impact of the native protein on CCC. Our data suggest that the anti-angiogenic activity of rP21 depends on the protein's direct interaction with the CXCR4 receptor. This capacity is likely related to the modulation of the expression of actin and angiogenesis-associated genes. Thus, our results indicate that T. cruzi P21 is an attractive target for the development of innovative therapeutic agents against CCC.
Assuntos
Inibidores da Angiogênese/metabolismo , Doença de Chagas/etiologia , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/metabolismo , Actinas/metabolismo , Inibidores da Angiogênese/farmacologia , Animais , Linhagem Celular , Proliferação de Células , Doença de Chagas/metabolismo , Doença de Chagas/parasitologia , Citoesqueleto/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Matriz Extracelular , Regulação da Expressão Gênica , Humanos , Camundongos , Modelos Biológicos , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Multimerização Proteica , Proteínas de Protozoários/farmacologia , Receptores CXCR4 , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologiaRESUMO
Host actin cytoskeleton polymerization has been shown to play an important role during Trypanosoma cruzi internalization into mammalian cell. The structure and dynamics of the actin cytoskeleton in cells are regulated by a vast number of actin-binding proteins. Here we aimed to verify the impact of AFAP-1L1, during invasion and multiplication of T. cruzi. Knocking-down AFAP-1L1 increased parasite cell invasion and intracellular multiplication. Thus, we have shown that the integrity of the machinery formed by AFAP-1L1 in actin cytoskeleton polymerization is important to hinder parasite infection.
Assuntos
Citoesqueleto de Actina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/farmacologia , Proteínas dos Microfilamentos/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Doença de Chagas/parasitologia , Citoplasma/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo , Trypanosoma cruzi/metabolismoRESUMO
In this study, the spinal nerves that constitute the lumbosacral plexus (LSP) were dissected in two species of South American wild canids (pampas fox-Pseudalopex gymnocercus, and crab-eating fox-Cerdocyon thous). The nerves origin and distribution in the pelvic limb were examined and compared with the LSP model of the dog described in the literature. The LSP was formed by whole ventral branches of L5 at L7 and S1, and a contribution of a one branch from S2, divided in three trunks. The trunk formed by union from L5-6 and S1 was divided into the cranial (cutaneus femoris lateralis nerve) medial (femoralis nerve) and lateral branches (obturatorius nerve). At the caudal part of the plexus, a thick branch, the ischiadicus plexus, was formed by contributions from L6-7 and S1-2. This root gives rise to the nerve branches which was disseminated to the pelvic limb (nerves gluteus cranial and gluteus caudal, cutaneus femoris caudalis and ischiadicus). The ischiadicus nerve was divided into fibularis communis and tibialis nerves. The tibialis nerve emits the cutaneus surae caudalis. The fibularis communis emits the cutaneus surae lateralis, fibularis superficialis and fibularis profundus. The pudendus nerve arises from S2 with contributions of one branch L7-S1 and one ramus of the cutaneus femoris lateralis. Still, one branch of S2 joins with S3 to form the rectales caudales nerve. These data provides an important anatomical knowledge of a two canid species of South American fauna, besides providing the effective surgical and clinical care of these animals.
Assuntos
Raposas/anatomia & histologia , Plexo Lombossacral/anatomia & histologia , Animais , Cães , Feminino , MasculinoRESUMO
The invasion of host cells by the intracellular protozoan Trypanosoma cruzi requires interactions with host cell molecules, and the replication of the parasite requires escape from a parasitophorous vacuole into the host cell cytosol. Galectin-3, a member of ß-galactosidase-binding lectin family, has numerous extracellular and intracellular functions. In this study, we investigated the role of galectin-3 during the invasion and intracellular trafficking of T. cruzi extracellular amastigotes (EAs). Endogenous galectin-3 from mouse peritoneal macrophages accumulated around the pathogen during cell invasion by EAs. In addition, galectin-3 accumulated around parasites after their escape from the parasitophorous vacuole. Thus, galectin-3 behaved as a novel marker of phagolysosome lysis during the infection of host cells by T. cruzi.