MECHANISMS OF NATURAL AND VACCINE-INDUCED RESISTANCE TO PARATUBERCULOSIS (Q3172991): Difference between revisions
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42°38'2.94"N, 5°58'17.11"W
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Revision as of 14:39, 9 October 2021
Project Q3172991 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | MECHANISMS OF NATURAL AND VACCINE-INDUCED RESISTANCE TO PARATUBERCULOSIS |
Project Q3172991 in Spain |
Statements
96,800.0 Euro
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193,600.0 Euro
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50.0 percent
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1 January 2019
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31 December 2021
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UNIVERSIDAD DE LEON
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42°38'2.94"N, 5°58'17.11"W
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24089
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LA PARATUBERCULOSIS ES UNA ENFERMEDAD INFECCIOSA, CAUSADA POR MYCOBACTERIUM AVIUM SUBSP PARATUBERCULOSIS (MAP) QUE AFECTA A LOS RUMIANTES, EN LOS QUE PROVOCA UNA ENTERITIS GRANULOMATOSA QUE CURSA CON DIARREA Y ADELGAZAMIENTO PROGRESIVO. NO EXISTE TRATAMIENTO EFECTIVO, Y ADEMAS DE LAS PERDIDAS DIRECTAS POR LA MUERTE DE ANIMALES, PRODUCE IMPORTANTES MERMAS ECONOMICAS POR EL DESCENSO EN LAS PRODUCCIONES QUE OCASIONA. ADEMAS, EN LOS ULTIMOS AÑOS, MAP ESTA COBRANDO UNA IMPORTANCIA CRECIENTE COMO POSIBLE ETIOLOGIA DE LA ENFERMEDAD DE CROHN HUMANA. EL CONTROL DE ESTA ENFERMEDAD ES DIFICIL. EN CONDICIONES NATURALES, HAY UN BUEN NUMERO DE ANIMALES QUE A PESAR DE ESTAR INFECTADOS, SON RESISTENTES AL DESARROLLO DE LA ENFERMEDAD CLINICA (FORMAS DE LATENCIA). LA VACUNACION, CONSIDERADO UN PROCEDIMIENTO EFECTIVO DE CONTROL DE LA ENFERMEDAD, NO PREVIENE LA INFECCION PERO CONFIERE A LOS ANIMALES INMUNIZADOS UNA RESPUESTA PROTECTORA QUE HACE QUE NO PROGRESE HACIA FORMAS CLINICAS. EL OBJETIVO DE ESTE PROYECTO ES INVESTIGAR CUALES SON LOS MECANISMOS PATOGENICOS RESPONSABLES DE ESA RESISTENCIA NATURAL O DE LA PROTECCION CONFERIDA POR LA VACUNA, PRINCIPALMENTE A NIVEL LOCAL (TEJIDO LINFOIDE INTESTINAL Y NODULOS LINFATICOS), DONDE SE PRODUCE LA INTERACCION HOSPEDADOR-PATOGENO. SE ESTUDIARAN CABRAS CON LA INFECCION NATURAL QUE MANIFIESTEN TODAS LAS FORMAS DE PRESENTACION DE LA ENFERMEDAD, Y SE LLEVARA A CABO UNA INFECCION EXPERIMENTAL EN CABRITOS VACUNADOS TANTO CON UNA VACUNA COMERCIAL DE INOCULACION SUBCUTANEA COMO CON UNA VACUNA DE ADMINISTRACION ORAL, DISEÑADA EN EL PROYECTO. ESTA ULTIMA SE COMPARARA CON LA VACUNA TRADICIONAL, PARA CONOCER SI EJERCE SU MISMA PROTECCION PERO SE PUEDE EVITAR EL EFECTO PERJUDICIAL DE INDUCIR REACCIONES CRUZADAS CON LAS PRUEBAS DE DIAGNOSTICO DE LA TUBERCULOSIS. PARA ELEGIR LA MEJOR DOSIS, SE LLEVARA A CABO UNA INFECCION EXPERIMENTAL PILOTO EN CONEJOS. EN LAS CABRAS NATURAL O EXPERIMENTALMENTE INFECTADAS, SE ESTUDIARAN LAS FORMAS LESIONALES PRESENTES, LA CARGA Y VIABILIDAD BACTERIANA Y LA RESPUESTA INMUNITARIA, TANTO A NIVEL PERIFERICO, INCLUYENDO LA CARACTERIZACION FENOTIPICA DE MACROFAGOS DERIVADOS DE MONOCITOS Y OTROS LEUCOCITOS, COMO, SOBRE TODO, A NIVEL LOCAL, EN MUESTRAS DE TEJIDO LINFOIDE INTESTINAL Y NODULOS LINFATICOS, EMPLEANDO DIFERENTES METODOLOGIAS, INCLUYENDO LA TECNICA RNA-SEQ DE SECUENCIACION MASIVA DEL TRANSCRIPTOMA, QUE PERMITIRA CONOCER LA EXPRESION DIFERENCIAL DE GENES EN LOS DISTINTOS TIPOS DE ANIMALES O LAS MODIFICACIONES INDUCIDAS POR LOS TIPOS DE VACUNA EMPLEADOS. (Spanish)
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PARATUBERCULOSIS IS AN INFECTIOUS DISEASE OF RUMINANTS CAUSED BY MYCOBACTERIUM AVIUM SUBSP PARATUBERCULOSIS (MAP). IT IS CHARACTERIZED BY A GRANULOMATOUS ENTERITIS THAT LEADS TO DIARRHOEA AND PROGRESSIVE LOSS OF WEIGHT. THERE IS NO EFFECTIVE TREATMENT. BESIDES ECONOMIC IMPACT DUE TO DIRECT LOSSES OF ANIMALS, THE MAIN EFFECT OF THE INFECTION ARE THE DECREASES IN THE MAIN PRODUCTIVE INDICATORS OF THE ANIMALS (MILK, FERTILITY¿). IN THE LAST YEARS, THE POSSIBLE ROLE OF MAP AS A CAUSATIVE AGENT OF HUMAN CROHN¿S DISEASE IS OF GREAT CONCERN. PARATUBERCULOSIS CONTROL IS DIFFICULT. IN NATURAL INFECTIONS, THERE IS A HIGH NUMBER OF ANIMALS THAT, DESPITE BEING INFECTED, NEVER DEVELOP CLINICAL DISEASE (RESISTANT OR LATENT FORMS). VACCINATION, CONSIDERED AS AN EFFECTIVE CONTROL METHOD, DOES NOT PREVENT INFECTION BUT CONFERS TO INFECTED ANIMALS A PROTECTIVE RESPONSE THAT PREVENT PROGRESSION TO CLINICAL FORMS. THE OBJECTIVE OF THIS PROJECT IS TO INVESTIGATE THE PATHOGENIC MECHANISMS RESPONSIBLE FOR THIS NATURAL RESISTANCE OR THE PROTECTION CONFERRED BY THE VACCINE, MAINLY AT THE LOCAL LEVEL (INTESTINAL LYMPHOID TISSUE AND LYMPH NODES), WHERE THE HOST-PATHOGEN INTERACTION TAKES PLACE. GOATS WITH THE NATURAL INFECTION SHOWING ALL THE FORMS OF PRESENTATION OF THE DISEASE WILL BE STUDIED, AND AN EXPERIMENTAL INFECTION WILL BE CARRIED OUT IN GOAT KIDS VACCINATED BOTH WITH A COMMERCIAL SUBCUTANEOUS INOCULATION VACCINE AND WITH AN ORAL VACCINE, DESIGNED IN THE PROJECT. THIS LAST ONE WILL BE COMPARED WITH THE TRADITIONAL VACCINE, TO KNOW IF IT EXERTS THE SAME PROTECTION BUT THE AVOIDING THE UNDESIRABLE CROSS REACTIONS THAT THE CURRENT VACCINES SHOW. TO SELECT THE BEST DOSE, A PILOT EXPERIMENTAL INFECTION IN RABBITS WILL BE CARRIED OUT. IN NATURAL OR EXPERIMENTALLY INFECTED GOATS, THE PRESENT LESION FORMS, THE BACTERIAL LOAD AND VIABILITY AND THE IMMUNE RESPONSE WILL BE STUDIED, BOTH AT THE PERIPHERAL LEVEL, INCLUDING THE PHENOTYPIC CHARACTERIZATION OF MACROPHAGES DERIVED FROM MONOCYTES AND OTHER LEUKOCYTES, AND, ABOVE ALL, AT THE LOCAL LEVEL, IN SAMPLES OF INTESTINAL LYMPHOID TISSUE AND LYMPH NODES, USING DIFFERENT METHODOLOGIES, INCLUDING THE RNA-SEQ TECHNIQUE OF MASSIVE TRANSCRIPTOME SEQUENCING, WHICH WILL ALLOW TO KNOW THE DIFFERENTIAL EXPRESSION OF GENES IN DIFFERENT TYPES OF ANIMALS OR THE MODIFICATIONS INDUCED BY THE TYPES OF VACCINE EMPLOYED. (English)
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León
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Identifiers
RTI2018-099496-B-I00
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