RESUMO
Trypanossoma cruzi (T. cruzi), the causative protozoan of Chagas disease (CD) invades many cell types, including central nervous system (CNS) cells triggering local lesions and neurological impact. Previous work from our group described NLRP3 inflammasomes as central effectors for the parasite control by macrophages. Recent evidences demonstrate that NLRP3 can be activated in CNS cells with controversial consequences to the control of infections and inflammatory pathologies. However, the relative contribution of NLRP3 in different cell types remains to be elucidated. In this article, we described an effector response mediated by NLRP3 that works on microglia but not on astrocytes to control T. cruzi infection. Despite T. cruzi ability to invade astrocytes and microglia, astrocytes were clearly more permissive to parasite replication. Moreover, the absence of NLRP3 renders microglia but not astrocytes more permissive to T. cruzi replication. In fact, microglia but not astrocytes were able to secrete NLRP3-dependent IL-1ß and NO in response to T. cruzi. Importantly, the pharmacological inhibition of iNOS with aminoguanidine resulted in a significant increase in the numbers of amastigotes found in microglia from wild-type but not from NLRP3-/- mice, indicating the importance of NLRP3-mediated NO secretion to the infection control by these cells. Taken together, our findings revealed that T. cruzi differentially activates NLRP3 inflammasomes in astrocytes and microglia and established a role for these platforms in the control of a protozoan infection by glial cells from CNS.
Assuntos
Astrócitos/parasitologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia , Óxido Nítrico/biossíntese , Trypanosoma cruzi/fisiologia , Animais , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , Microglia/parasitologiaRESUMO
The protozoan Trypanosoma cruzi is the etiological agent of Chagas disease. In immunosuppressed individuals, as it occurs in the coinfection with human immunodeficiency virus (HIV), the central nervous system may be affected. In this regard, reactivation of Chagas disease is severe and often lethal, and it accounts for meningoencephalitis. Astrocytes play a crucial role in the environment maintenance of healthy neurons; however, they can host HIV and T. cruzi. In this report, human astrocytes were infected in vitro with both genetically modified-pathogens to express alternative fluorophore. As evidenced by fluorescence microscopy and flow cytometry, HIV and T. cruzi coexist in the same astrocyte, likely favoring reciprocal interactions. In this context, lower rates of cell death were observed in both T. cruzi monoinfected-astrocytes and HIV-T. cruzi coinfection in comparison with those infected only with HIV. The level of HIV replication is significantly diminished under T. cruzi coinfection, but without affecting the infectivity of the HIV progeny. This interference with viral replication appears to be related to the T. cruzi multiplication rate or its increased intracellular presence but does not require their intracellular cohabitation or infected cell-to-cell contact. Among several Th1/Th2/Th17 profile-related cytokines, only IL-6 was overexpressed in HIV-T. cruzi coinfection exhibiting its cytoprotective role. This study demonstrates that T. cruzi and HIV are able to coinfect astrocytes thus altering viral replication and apoptosis.
Assuntos
Apoptose , Astrócitos/imunologia , Doença de Chagas/complicações , Coinfecção , Infecções por HIV/complicações , Replicação Viral/fisiologia , Apoptose/efeitos dos fármacos , Astrócitos/parasitologia , Astrócitos/virologia , Morte Celular , Linhagem Celular , Doença de Chagas/imunologia , Doença de Chagas/virologia , Citocinas/metabolismo , HIV/fisiologia , Infecções por HIV/imunologia , Herpesvirus Humano 2/fisiologia , Humanos , Interleucina-6 , Nitroimidazóis/farmacologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Trypanosoma cruzi/genética , Trypanosoma cruzi/imunologia , Trypanosoma cruzi/fisiologiaRESUMO
The inflammatory cytokine interferon-gamma (IFNγ) is crucial for immunity against intracellular pathogens such as the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease (CD). IFNγ is a pleiotropic cytokine which regulates activation of immune and non-immune cells; however, the effect of IFNγ in the central nervous system (CNS) and astrocytes during CD is unknown. Here we show that parasite persists in the CNS of C3H/He mice chronically infected with the Colombian T. cruzi strain despite the increased expression of IFNγ mRNA. Furthermore, most of the T. cruzi-bearing cells were astrocytes located near IFNγ+ cells. Surprisingly, in vitro experiments revealed that pretreatment with IFNγ promoted the infection of astrocytes by T. cruzi increasing uptake and proliferation of intracellular forms, despite inducing increased production of nitric oxide (NO). Importantly, the effect of IFNγ on T. cruzi uptake and growth is completely blocked by the anti-tumor necrosis factor (TNF) antibody Infliximab and partially blocked by the inhibitor of nitric oxide synthesis L-NAME. These data support that IFNγ fuels astrocyte infection by T. cruzi and critically implicate IFNγ-stimulated T. cruzi-infected astrocytes as sources of TNF and NO, which may contribute to parasite persistence and CNS pathology in CD.
Assuntos
Astrócitos/efeitos dos fármacos , Astrócitos/parasitologia , Doença de Chagas/fisiopatologia , Interferon gama/farmacologia , Animais , Astrócitos/metabolismo , Células Cultivadas , Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Citocinas/metabolismo , Feminino , Imuno-Histoquímica , Infliximab/farmacologia , Interferon gama/genética , Interferon gama/metabolismo , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Trypanosoma cruzi/crescimento & desenvolvimentoRESUMO
Trypanosoma cruzi's trypomastigotes are highly active and their incessant motility seems to be important for mammalian host cell infection. The kinetoplastid membrane protein-11 (KMP-11) is a protein expressed in all parasite stages, which induces a cellular and humoral immune response in the infected host, and is hypothesized to participate in the parasite's motility. An N-terminal peptide from KMP-11, termed K1 or TcTLE, induced polyclonal antibodies that inhibit parasitic invasion of Vero cells. The goal of this study was to evaluate the motility and infectivity of T. cruzi when exposed to polyclonal anti-TcTLE antibodies. Rabbits were immunized with TcTLE peptide along with FIS peptide as an immunomodulator. ELISA assay results showed that post-immunization sera contained high titers of polyclonal anti-TcTLE antibodies, which were also reactive against the native KMP-11 protein and live parasites as detected by immunofluorescence and flow cytometry assays. Trypomastigotes of T. cruzi were incubated with pre- or post-immunization sera, and infectivity to human astrocytes was assessed by Giemsa staining/light microscope and flow cytometry using carboxyfluorescein diacetate succinimidyl ester (CFSE) labeled parasites. T. cruzi infection in astrocytes decreased approximately by 30% upon incubation with post-immunization sera compared with pre-immunization sera. Furthermore, trypomastigotes were recorded by video microscopy and the parasite's flagellar speed was calculated by tracking the flagella. Trypomastigotes exposed to post-immunization sera had qualitative alterations in motility and significantly slower flagella (45.5 µm/s), compared with those exposed to pre-immunization sera (69.2 µm/s). In summary, polyclonal anti-TcTLE serum significantly reduced the parasite's flagellar speed and cell infectivity. These findings support that KMP-11 could be important for parasite motility, and that by targeting its N-terminal peptide infectivity can be reduced.
Assuntos
Anticorpos Antiprotozoários/imunologia , Astrócitos/parasitologia , Proteínas de Protozoários/imunologia , Trypanosoma cruzi/fisiologia , Animais , Antígenos de Protozoários/imunologia , Linhagem Celular Tumoral , Citometria de Fluxo , Imunofluorescência , Humanos , Masculino , Microscopia de Vídeo , Movimento , Coelhos , Trypanosoma cruzi/imunologiaRESUMO
Astrocytes play a vital role in neuronal protection, homeostasis, vascular interchange and the local immune response. Some viruses and parasites can cross the blood-brain barrier and infect glia. Trypanosoma cruzi, the aetiological agent of Chagas disease, can seriously compromise the central nervous system, mainly in immune-suppressed individuals, but also during the acute phase of the infection. In this report, the infective capacity of T. cruzi in a human astrocyte tumour-derived cell line was studied. Astrocytes exposed to trypomastigotes (1:10 ratio) produced intracellular amastigotes and new trypomastigotes emerged by day 4 post-infection (p.i.). At day 6 p.i., 93% of the cells were infected. Using flow cytometry, changes were observed in both the expression of major histocompatibility complex class I and II molecules and the chemokine secretion pattern of astrocytes exposed to the parasite. Blocking the low-density lipoprotein receptor on astrocytes did not reduce parasite intracellular infection. Thus, T. cruzi can infect astrocytes and modulate the immune response during central nervous system infection.
Assuntos
Astrócitos/parasitologia , Astrocitoma/parasitologia , Imunidade Celular/imunologia , Trypanosoma cruzi/fisiologia , Astrocitoma/imunologia , Barreira Hematoencefálica/imunologia , Linhagem Celular Tumoral , Humanos , Complexo Principal de Histocompatibilidade/imunologia , Fatores de TempoRESUMO
Astrocytes play a vital role in neuronal protection, homeostasis, vascular interchange and the local immune response. Some viruses and parasites can cross the blood-brain barrier and infect glia. Trypanosoma cruzi, the aetiological agent of Chagas disease, can seriously compromise the central nervous system, mainly in immune-suppressed individuals, but also during the acute phase of the infection. In this report, the infective capacity of T. cruzi in a human astrocyte tumour-derived cell line was studied. Astrocytes exposed to trypomastigotes (1:10 ratio) produced intracellular amastigotes and new trypomastigotes emerged by day 4 post-infection (p.i.). At day 6 p.i., 93% of the cells were infected. Using flow cytometry, changes were observed in both the expression of major histocompatibility complex class I and II molecules and the chemokine secretion pattern of astrocytes exposed to the parasite. Blocking the low-density lipoprotein receptor on astrocytes did not reduce parasite intracellular infection. Thus, T. cruzi can infect astrocytes and modulate the immune response during central nervous system infection.
Assuntos
Humanos , Astrócitos/parasitologia , Astrocitoma/parasitologia , Imunidade Celular/imunologia , Trypanosoma cruzi/fisiologia , Astrocitoma/imunologia , Barreira Hematoencefálica/imunologia , Linhagem Celular Tumoral , Complexo Principal de Histocompatibilidade/imunologia , Fatores de TempoRESUMO
Toxoplasma gondii invades any nucleated cell, but different replication speed and effects on survival/apoptosis processes have been found depending on cell type. There are scarce and controversial results regarding the effect of this parasite on host cell apoptosis within the brain. The invasion and replication of T. gondii RH strain within newborn mouse astrocytes were evaluated in the present work. At 4 hpi>90% cells were infected and harbored one to three parasitophorous vacuoles with one tazchyzoite/vacuole. Cell culture massive destruction started after 24 h of exposure, when the parasite already replicated, with a duplication time of around 5 h. The effect of T. gondii infection on apoptosis was also evaluated by changes in some anti- and pro-apoptotic markers. At early infection times decreased Bcl-2, Survivin and PUMA and increased Noxa expression was found, although Survivin and Noxa mRNA levels reverted towards an anti-apoptotic phenotype after 6 h. Caspases 3/7 activity decreased three hours after infection, although it returned to normal levels thereafter. This enzymatic activity was strongly stimulated by Cisplatin (anti-neoplasic drug) but it was inhibited by previous T. gondii infection. Likewise, parasite invasion prevented PARP-1 fragmentation and cell apoptosis induced by the same drug. In conclusion, astrocytes seem to activate some apoptosis signals shortly after infection, but the parasite takes control of the cell and inhibits programmed death for up to 24 h, until it replicates, egresses and generates cellular destruction.
Assuntos
Proteínas Reguladoras de Apoptose/genética , Astrócitos/parasitologia , Proteínas de Protozoários/genética , Toxoplasma/fisiologia , Animais , Animais Recém-Nascidos , Antineoplásicos/farmacologia , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Encéfalo/citologia , Caspases/metabolismo , Cisplatino/farmacologia , Feminino , Regulação da Expressão Gênica , Genes bcl-2/genética , Proteína Glial Fibrilar Ácida , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas de Protozoários/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Organismos Livres de Patógenos Específicos , Survivina , Toxoplasma/crescimento & desenvolvimento , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
Toxoplasma gondii is a cosmopolitan protozoan which infects all homoeothermic species, including humans. This parasite may cause severe neurological problems in congenitally infected newborns or immunocompromised individuals, but it also provokes psychiatric and neurological disorders as well as behavioural and sensory deficit. There is controversy regarding the effect of T. gondii upon astrocytes, which may serve as parasite proliferation recipients or protective immune response activators within the central nervous system. This apparent contradiction could partially be due to the infection degree obtained in the different experiments reported. Thus, we decided to systematically review the in vitro models used to study these phenomena. Fifteen articles from which direct invasion and replication data could be gathered were found. Very heterogeneous results emerged, mainly due to diversity of models in relation to parasite strain (virulence), host species, parasite dose and evaluation times after infection. Also, the results were measured in diverse ways, i.e. some reported percent infected cells, while others informed parasites pervacuole or cell, or parasitic vacuoles per cell. Very few conclusions could be drawn, among them that human astrocytoma cell lines and mouse astrocytes seem more susceptible to infection and less resistant to tachyzoite proliferation than human primary culture astrocytes. The present study supports the need to reanalyse T. gondii astrocyte invasion and replication processes, especially with the use of actual technology, which allows detailed mechanistic studies.
Assuntos
Astrócitos/parasitologia , Toxoplasma/crescimento & desenvolvimento , Toxoplasma/patogenicidade , Animais , Técnicas de Cultura de Células , Células Cultivadas , Humanos , Camundongos , Toxoplasma/imunologiaRESUMO
This study aimed to characterize astrocytic and microglial response in the central nervous system (CNS) of equines experimentally infected with T. evansi. The experimental group comprised males and females with various degrees of crossbreeding, ages between four and seven years. The animals were inoculated intravenously with 10(6) trypomastigotes of T. evansi originally isolated from a naturally infected dog. All equines inoculated with T. evansi were observed until they presented symptoms of CNS disturbance, characterized by motor incoordination of the pelvic limbs, which occurred 67 days after inoculation (DAI) and 124 DAI. The animals in the control group did not present any clinical symptom and were observed up to the 125th DAI. For this purpose the HE histochemical stain and the avidin biotin peroxidase method was used. Lesions in the CNS of experimentally infected horses were those of a wide spread non suppurative meningoencephalomyelitis.The severity of lesions varied in different parts of the nervous system, reflecting an irregular distribution of inflammatory vascular changes. The infiltration of mononuclear cells was associated with anisomorphic gliosis and reactive microglia was identified. The intensity of the astrocytic response in the CNS of the equines infected by T. evansi characterizes the importance of the performance of these cells in this trypanosomiasis. The characteristic gliosis observed in the animals in this experiment suggests the ability of these cells as mediators of immune response. The parasite, T. evansi, was not identified in the nervous tissues.
Assuntos
Astrócitos/patologia , Encéfalo/patologia , Infecções Protozoárias do Sistema Nervoso Central/veterinária , Doença de Chagas/veterinária , Doenças dos Cavalos/patologia , Microglia/patologia , Trypanosoma/imunologia , Animais , Astrócitos/parasitologia , Encéfalo/imunologia , Infecções Protozoárias do Sistema Nervoso Central/imunologia , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/patologia , Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Doença de Chagas/patologia , Doença Crônica , Encefalomielite/imunologia , Encefalomielite/parasitologia , Encefalomielite/patologia , Encefalomielite/veterinária , Feminino , Doenças dos Cavalos/imunologia , Doenças dos Cavalos/parasitologia , Cavalos , Masculino , Meningoencefalite/imunologia , Meningoencefalite/parasitologia , Meningoencefalite/patologia , Meningoencefalite/veterinária , Microglia/parasitologia , Índice de Gravidade de Doença , Trypanosoma/classificaçãoRESUMO
This study aimed to characterize astrocytic and microglial response in the central nervous system (CNS) of equines experimentally infected with T. evansi. The experimental group comprised males and females with various degrees of crossbreeding, ages between four and seven years. The animals were inoculated intravenously with 10(6) trypomastigotes of T. evansi originally isolated from a naturally infected dog. All equines inoculated with T. evansi were observed until they presented symptoms of CNS disturbance, characterized by motor incoordination of the pelvic limbs, which occurred 67 days after inoculation (DAI) and 124 DAI. The animals in the control group did not present any clinical symptom and were observed up to the 125th DAI. For this purpose the HE histochemical stain and the avidin biotin peroxidase method was used. Lesions in the CNS of experimentally infected horses were those of a wide spread non suppurative meningoencephalomyelitis.The severity of lesions varied in different parts of the nervous system, reflecting an irregular distribution of inflammatory vascular changes. The infiltration of mononuclear cells was associated with anisomorphic gliosis and reactive microglia was identified. The intensity of the astrocytic response in the CNS of the equines infected by T. evansi characterizes the importance of the performance of these cells in this trypanosomiasis. The characteristic gliosis observed in the animals in this experiment suggests the ability of these cells as mediators of immune response. The parasite, T. evansi, was not identified in the nervous tissues.
Este estudo objetivou caracterizar a participação astrocítica e microglial no sistema nervoso central (SNC) de eqüinos experimentalmente infectados com T. evansi. O grupo experimental foi formado por machos e fêmeas com vários graus de cruzamentos e idade variando entre quatro e sete anos. Os animais foram inoculados com 10(6) tripomastigotas de T. evansi, originalmente isolada de um cão infectado naturalmente. Todos os eqüinos inoculados foram observados até o aparecimento dos sintomas neurológicos, caracterizados por incoordenação motora dos membros pélvicos, o qual ocorreu entre 67 e 124 dias após a inoculação (DPI). Os animais do grupo controle não apresentaram sinais clínicos e foram observados até o 125º DPI. Para este propósito, foram utilizados os métodos histoquímicos (HE) e imunoistoquímicos do complexo avidina-biotina peroxidase (ABC). A lesão no sistema nervoso central (SNC) dos eqüinos infectados com T. evansi foi caracterizada como meningoencefalomielite não supurativa. A gravidade das lesões variou em diferentes segmentos do SNC, refletindo distribuição irregular das alterações vasculares. Infiltrado perivascular e meníngeo foi associado a gliose anisomórfica e microgliose reativa. A intensidade da resposta astrocítica no SNC dos equinos infectados com T. evansi caracteriza a importância da performance destas células nas tripanossomíases. A gliose observada nos animais deste experimento sugerem a habilidade destas células como mediadoras da resposta imune. T. evansi não foi identificado no parênquima do SNC.
Assuntos
Animais , Feminino , Masculino , Astrócitos/patologia , Encéfalo/patologia , Infecções Protozoárias do Sistema Nervoso Central/veterinária , Doença de Chagas/veterinária , Doenças dos Cavalos/patologia , Microglia/patologia , Trypanosoma/imunologia , Astrócitos/parasitologia , Encéfalo/imunologia , Doença Crônica , Infecções Protozoárias do Sistema Nervoso Central/imunologia , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/patologia , Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Doença de Chagas/patologia , Encefalomielite/imunologia , Encefalomielite/parasitologia , Encefalomielite/patologia , Encefalomielite/veterinária , Cavalos , Doenças dos Cavalos/imunologia , Doenças dos Cavalos/parasitologia , Meningoencefalite/imunologia , Meningoencefalite/parasitologia , Meningoencefalite/patologia , Meningoencefalite/veterinária , Microglia/parasitologia , Índice de Gravidade de Doença , Trypanosoma/classificaçãoRESUMO
The protozoan Neospora caninum has a veterinary importance because it causes abortion in cattle and neuromuscular alterations in dogs. We infected rat astrocytes, in vitro, with different concentrations of N. caninum. Astrocytes responded to infection by producing the pro-inflammatory cytokine TNF-alpha and the neurotoxic-free radical NO, 24 and 72 h post-infection. These data suggest that astrocytes, which are essential for brain function, are targets for the parasite and this represents a practical and valid model to study the effects of N. caninum on the CNS.
Assuntos
Astrócitos/parasitologia , Doenças do Sistema Nervoso Central/parasitologia , Doenças do Sistema Nervoso Central/veterinária , Coccidiose/imunologia , Neospora/imunologia , Animais , Astrócitos/imunologia , Astrócitos/metabolismo , Células Cultivadas , Doenças do Sistema Nervoso Central/imunologia , Doenças do Sistema Nervoso Central/metabolismo , Chlorocebus aethiops , Coccidiose/parasitologia , Coccidiose/veterinária , Imuno-Histoquímica/veterinária , Nitritos/metabolismo , Ratos , Fator de Necrose Tumoral alfa/metabolismo , Células VeroRESUMO
The effect of Neospora caninum, a parasite that causes abortion and neuromuscular changes, has been investigated on a major population of neural cells, the astrocytes. Highly enriched astroglial primary cultures obtained from neonatal rats were infected after 21 days of culture. Astroglial reactivity, IL-10 and IFN-gamma expression, and cell viability (lactate dehydrogenase activity, metabolization of tetrazolium salt, and trypan blue exclusion assay) have been investigated after 24 and 72 h of infection. Astroglial hypertrophy, gliofilament reorganization, metabolic changes suggesting hypoxia and a strong IL-10 release have been observed in the infected cells. These results show that neural cells are targets for the parasite and that astrocytes may contribute to the CNS immune response to the parasite.
Assuntos
Astrócitos/imunologia , Astrócitos/parasitologia , Interleucina-10/biossíntese , Neospora/imunologia , Animais , Animais Recém-Nascidos , Astrócitos/enzimologia , Sobrevivência Celular , Células Cultivadas , Imuno-Histoquímica , Interferon gama/biossíntese , Lactato Desidrogenases/metabolismo , RatosRESUMO
The maintenance of a benign chronic Toxoplasma gondii infection is mainly dependent on the persistent presence of gamma interferon (IFN-gamma) in the central nervous system (CNS). However, IFN-gamma-activated microglia are paradoxically involved in parasitism control and in tissue damage during a broad range of CNS pathologies. In this way, nitric oxide (NO), the main toxic metabolite produced by IFN-gamma-activated microglia, may cause neuronal injury during T. gondii infection. Despite the potential NO toxicity, neurodegeneration is not a common finding during chronic T. gondii infection. In this work, we describe a significant down-modulation of NO production by IFN-gamma-activated microglia in the presence of conditioned medium of T. gondii-infected astrocytes (CMi). The inhibition of NO production was paralleled with recovery of neurite outgrowth when neurons were cocultured with IFN-gamma-activated microglia in the presence of CMi. Moreover, the modulation of NO secretion and the neuroprotective effect were shown to be dependent on prostaglandin E(2) (PGE(2)) production by T. gondii-infected astrocytes and autocrine secretion of interleukin-10 (IL-10) by microglia. These events were partially eliminated when infected astrocytes were treated with aspirin and cocultures were treated with anti-IL-10 neutralizing antibodies and RP-8-Br cyclic AMP (cAMP), a protein kinase A inhibitor. Further, the modulatory effects of CMi were mimicked by the presence of exogenous PGE(2) and by forskolin, an adenylate cyclase activator. Altogether, these data point to a T. gondii-triggered regulatory mechanism involving PGE(2) secretion by astrocytes and cAMP-dependent IL-10 secretion by microglia. This may reduce host tissue inflammation, thus avoiding neuron damage during an established Th1 protective immune response.
Assuntos
Astrócitos/imunologia , Meios de Cultivo Condicionados/farmacologia , Microglia/efeitos dos fármacos , Neurônios/imunologia , Óxido Nítrico/biossíntese , Toxoplasma/patogenicidade , Animais , Astrócitos/parasitologia , Células Cultivadas , Técnicas de Cocultura , AMP Cíclico/biossíntese , Dinoprostona/biossíntese , Regulação para Baixo/efeitos dos fármacos , Interferon gama/imunologia , Interleucina-10/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Microglia/imunologia , Neurônios/patologia , SolubilidadeRESUMO
The infection and multiplication of Toxoplasma gondii and Trypanosoma cruzi were compared in primary cultures of white rat, mouse and hamster astrocytes. These cells were cultured on cover slides and infected with T. gondii tachyzoites or T. cruzi blood trypomastigotes. Results show that hamster astrocytes are more susceptible to the multiplication of both parasites than rat and mouse cells. There was no statistical difference between the T. gondii infection in rat and mouse astrocytes (p < 0.05), and this suggests an important role of other mechanisms or cells in the white rat natural resistance to this parasite. Because the hamster astrocytes are less resistant to these parasites multiplication and not necessarily to the invasion, any difference observed could be due to an intracellular effect: hamster brain astrocytes favor survival and multiplication of these parasites.
Assuntos
Astrócitos/parasitologia , Toxoplasma/crescimento & desenvolvimento , Trypanosoma cruzi/crescimento & desenvolvimento , Animais , Técnicas de Cultura de Células , Cricetinae , Interações Hospedeiro-Parasita , Mesocricetus , Camundongos , Ratos , Ratos Sprague-Dawley , Especificidade da Espécie , Fatores de TempoRESUMO
In neurocysticercosis, the nervous tissue surrounding the brain lesion is affected as a consequence of the local immune response induced by a Taenia solium metacestode. In this study, a histological and immunohistochemical analysis of five brain specimens from patients with neurocysticercosis revealed a proinflammatory activity reflected by an apparently altered blood-brain barrier permeability, secretion of pro-inflammatory cytokines, and up-regulation of molecules associated with antigen presentation. There were also anti-inflammatory cytokines, as well as an active wound-healing process reflected by angiogenesis, collagen deposition and glial scar formation. This immune response displayed by the nervous tissue adjacent to chronic neurocysticercosis lesions appeared to be contributing to the local tissue damage, and hence, may be fundamental in the pathology of NCC.
Assuntos
Neurocisticercose/imunologia , Neurocisticercose/patologia , Taenia/imunologia , Animais , Astrócitos/parasitologia , Barreira Hematoencefálica/imunologia , Química Encefálica/imunologia , Citocinas/análise , Fator 2 de Crescimento de Fibroblastos/análise , Humanos , Macrófagos/parasitologia , Mastócitos/patologia , Microglia/parasitologia , Células Th1/imunologia , Células Th2/imunologiaRESUMO
Chagas' disease, caused by the protozoan Trypanosoma cruzi, is characterized by an acute phase in which parasites circulate in the blood and proliferate in several cell types, especially muscle cells. A life-long chronic phase follows the acute phase. In young patients, the acute phase is more severe, and meningoencephalitis frequently occurs in children before 2 years of age. Parasites have been rarely observed in neurons but their presence inside glial cells has been reported without characterization of the glial cell type. The cells involved in the brain reaction to the parasites and the time course of this reaction remain to be studied. Therefore, using suckling and juvenile rats and different T. cruzi populations, we aimed at determining the brain target for parasite proliferation and the cells involved in the brain reaction. Around the middle of the acute phase, histological and ultrastructural findings indicated that T. cruzi proliferates in astrocytes, forming nests devoid of enclosing membrane as described for non-glial cells. The brain nodular reaction comprised astrocytes, microglia, macrophages and neutrophils. Resting microglia was devoid of parasites in contrast to macrophages and neutrophils that probably participate in parasite removal. Suckling animals were significantly more affected, the numbers of nests and nodules varying with inoculum size. Histoquantitative analysis showed higher number of nests at the parasitemic peak (day 13) and drastic fall at day 20 post-inoculation. The highest number of nodules occurred at day 20 with drastic reduction at day 30. Recovery from histopathological alterations occurred even in surviving younger animals.