RESUMO
Venezuelan equine encephalitis virus (VEE) produces an acute infection in humans and induces a well-characterized cytopathic effect in neurons of the central nervous system (CNS). However, little is known about the role of glial cells in response to VEE infection of the CNS. Our results demonstrate that VEE is capable of a productive infection in primary astrocyte cultures and that this infection is cytotoxic. Further, there were significant differences in the growth kinetics comparing virulent and attenuated strains of VEE. Additionally, VEE infection of astrocyte cultures induced gene expression of two neuro-immune modulators, tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS). Assays for TNF-alpha protein and nitric oxide (NO) demonstrated high levels of TNF-alpha protein and low levels of NO in response to VEE infection of astrocytes. These observations suggest an important role of astrocytes in this virus-induced encephalitis, and that interactions between astrocytes, other glial cells, and neurons may be important in VEE pathogenesis. Such interactions, which could impact neuronal survival, may include loss of functional changes in astrocytes or, alternatively, their production of neurotoxic molecules.
Assuntos
Astrócitos/virologia , Vírus da Encefalite Equina Venezuelana/fisiologia , Animais , Astrócitos/metabolismo , Células Cultivadas , Vírus da Encefalite Equina Venezuelana/patogenicidade , Encefalomielite Equina Venezuelana/patologia , Óxido Nítrico Sintase/análise , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo , Virulência , Replicação ViralRESUMO
The susceptibility of 12 strains of inbred mice representing a broad genetic spectrum to infection of Leishmania braziliensis, L. mexicana and L. aethiopica was determined. Levels of susceptibility were evaluated by gross morphology of lesions, evidence of resolution, persistence of parasites at the site of inoculation, and visceralization to the spleen or liver following inoculation in noses. Very different patterns of responses were noted among the infections with the three species of Leishmania. Among the strains of inbred mice infected with L. braziliensis, patterns of cutaneous lesion development indicated a broad range of susceptibilities and responses. Two strains of inbred mice (AKR/J and CBA/J) showed only a slight and transient swelling of the nose. The SWR/J, C57L/J, A/J, A/HeJ and DBA/1J showed initial swellings or nodules which eventually resolved. In contrast, the BALB/cJ mice were ranked as most susceptible, based on progressive dermal lesions and visceralization. Four strains of inbred mice (C3H/HeJ, C57BL/6J, CBA/J and CBA/CaJ) showed no evidence of infection. Lesion development in most strains of inbred mice infected with L. mexicana occurred later than with L. braziliensis but was then more rapidly progressive with no indication of resolution. Two strains (C3H/HeJ and C57BL/6J) showed no evidence of infection. Only slight swellings of the nose were seen in the 12 strains of inbred mice infected with L. aethiopica; however, parasites were isolated by culture from apparently normal noses in five groups (A/HeJ, AKR/J, BALB/cJ, DBA/2J and SWR/J).
Assuntos
Leishmaniose Mucocutânea/parasitologia , Leishmaniose/parasitologia , Animais , Modelos Animais de Doenças , Suscetibilidade a Doenças , Leishmaniose/imunologia , Leishmaniose/patologia , Leishmaniose Mucocutânea/imunologia , Leishmaniose Mucocutânea/patologia , Camundongos , Camundongos EndogâmicosRESUMO
Thirty-four Mystromys albicaudatus were injected intradermally with Leishmania braziliensis promastigotes and examined and killed during a 12-week period. All animals developed single cutaneous lesions at the sites of inoculation that began as a papular thickening in the dermis and progressed to a 2.0 cm crateriform ulcer. The histopathology of these lesions was characterized by granuloma formation and diffuse infiltrates of lymphocytes and plasma cells. Parasites were most frequently observed in vacuolated macrophages immediately underlying the necrotic debris of the ulcer. Histiocytes in which amastigotes were not identified were noted in aggregates at the margins of the inflammation. Russell's bodies were observed at 6 weeks post-infection, and discrete lymphocytic infiltrates bordered the inflammation at 12 weeks post-infection. It is suggested that M. albicaudatus is an excellent model of American cutaneous leishmaniasis.