RESUMO
Optical neuritis (ON) is characterized by inflammation of the optic nerve, and is one of the first clinical signs of multiple sclerosis (MS). Experimental autoimmune encephalomyelitis (EAE) is the animal model used to study MS and ON. The present study evaluated the induction, development and progression of ON using an EAE model induced by 100 µg or 300 µg of MOG35-55. An EAE model was induced in C57BL/6 mice by tail base injection of 100 µg or 300 µg of MOG35-55 in complete Freund's adjuvant, supplemented with Mycobacterium tuberculosis. On the day of injection and 48 h later, animals received intraperitoneally 300 ng of pertussis toxin. On days 7, 10, 14, 21 and 58 the optic nerve was dissected for histological analysis, production of CCL5 and immunohistochemical detection of CD4 and CD8. The histological changes observed in the optic nerves consisted of inflammatory cell infiltrates showing varying degrees of ON in the two groups. The onset of ON in the 300 µg of MOG35-55 group was coincident with higher production of CCL5, on day 10 after induction. However, the 100 µg MOG35-55 group showed more intense inflammatory infiltrate on day 14 after induction, with higher amounts of CD4 and CD8, reaching an excessive demyelination process on days 21 and 58 after induction. The results suggest that two different concentrations of MOG35-55 lead to different forms of evolution of optic neuritis.
Assuntos
Encefalomielite Autoimune Experimental/imunologia , Mediadores da Inflamação/administração & dosagem , Mediadores da Inflamação/fisiologia , Glicoproteína Mielina-Oligodendrócito/administração & dosagem , Neurite Óptica/imunologia , Neurite Óptica/patologia , Animais , Antígenos CD4/biossíntese , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Antígenos CD8/biossíntese , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Quimiocina CCL5/biossíntese , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Encefalomielite Autoimune Experimental/patologia , Feminino , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/imunologia , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Glicoproteína Mielina-Oligodendrócito/fisiologia , Neurite Óptica/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/fisiologiaRESUMO
OBJECTIVE: This study aimed to determine whether Mycobacterium bovis Bacillus Calmette-Guérin (BCG) treatment can reverse an established allergic airway inflammation in a BALB/c mouse model of ovalbumin (OVA)-induced airway inflammation. METHODS: OVA sensitized BALB/c mice were challenged with aerosolized OVA on days 28 to 30, 34, 41 and 63. Mice were intranasal treated with BCG on days 35 and 42. Twenty-four hours after the last challenge, blood samples were collected to detect anti-OVA immunoglobulin isotypes, and bronchoalveolar lavage (BAL) was harvested for cell count. Additionally, lungs were collected for histological analysis, detection of the eosinophil peroxidase (EPO) activity and measurement of cytokines and CCL11. The expression of CTLA-4, Foxp3 and IL-10 was also determined in lung tissue by flow cytometry. RESULTS: BCG treatment was able to inhibit an established allergic Th2-response, by decreasing the allergen-induced eosinophilic inflammation, EPO activity, levels of CCL11 and IL-4, serum levels of IgE and IgG1. Mycobacteria treatment increased lung levels of IFN-γ, IL-10 and TGF-ß, and expressions of Foxp3 and CTLA-4 in CD4(+)T cells. Additionally, an increased production of IL-10 by CD8(+) T cells was observed, even though no detectable changes in CD4(+)IL-10(+) was noticed. CONCLUSION: BCG treatment inhibits features of allergic airway inflammation and the results suggest that the mechanism underlying the down-regulatory effects of BCG on OVA-induced airway inflammation appear to be associated with the induction of both Th1 and T regulatory immune responses.
Assuntos
Antialérgicos/administração & dosagem , Vacina BCG/administração & dosagem , Regulação para Baixo/imunologia , Mycobacterium bovis/imunologia , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Hipersensibilidade Respiratória/imunologia , Células Th2/imunologia , Animais , Antialérgicos/imunologia , Vacina BCG/imunologia , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Feminino , Imunoglobulina E/biossíntese , Imunoglobulina G/biossíntese , Inflamação/microbiologia , Inflamação/patologia , Inflamação/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Hipersensibilidade Respiratória/patologia , Hipersensibilidade Respiratória/prevenção & controle , Células Th2/efeitos dos fármacos , Células Th2/microbiologiaRESUMO
The presence of intestinal helminths can down-regulate the immune response required to control mycobacterial infection. BALB/c mice infected with Mycobacterium bovis following an infection with the intestinal helminth Strongyloides venezuelensis showed reduced interleukin-17A production by lung cells and increased bacterial burden. Also, small granulomas and a high accumulation of cells expressing the inhibitory molecule CTLA-4 were observed in the lung. These data suggest that intestinal helminth infection could have a detrimental effect on the control of tuberculosis (TB) and render coinfected individuals more susceptible to the development of TB.
Assuntos
Interleucina-17/biossíntese , Enteropatias Parasitárias/imunologia , Infecções por Mycobacterium/imunologia , Mycobacterium bovis/imunologia , Strongyloides/imunologia , Estrongiloidíase/imunologia , Animais , Carga Bacteriana/métodos , Coinfecção/complicações , Coinfecção/imunologia , Coinfecção/patologia , Suscetibilidade a Doenças , Enteropatias Parasitárias/complicações , Enteropatias Parasitárias/patologia , Pulmão/microbiologia , Pulmão/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Mycobacterium/complicações , Infecções por Mycobacterium/patologia , Estrongiloidíase/complicações , Estrongiloidíase/patologiaRESUMO
The presence of intestinal helminths can down-regulate the immune response required to control mycobacterial infection. BALB/c mice infected with Mycobacterium bovis following an infection with the intestinal helminth Strongyloides venezuelensis showed reduced interleukin-17A production by lung cells and increased bacterial burden. Also, small granulomas and a high accumulation of cells expressing the inhibitory molecule CTLA-4 were observed in the lung. These data suggest that intestinal helminth infection could have a detrimental effect on the control of tuberculosis (TB) and render coinfected individuals more susceptible to the development of TB.