RESUMEN
Influenza A virus (IAV) activates ZBP1-initiated RIPK3-dependent parallel pathways of necroptosis and apoptosis in infected cells. Although mice deficient in both pathways fail to control IAV and succumb to lethal respiratory infection, RIPK3-mediated apoptosis by itself can limit IAV, without need for necroptosis. However, whether necroptosis, conventionally considered a fail-safe cell death mechanism to apoptosis, can restrict IAV-or indeed any virus-in the absence of apoptosis is not known. Here, we use mice selectively deficient in IAV-activated apoptosis to show that necroptosis drives robust antiviral immune responses and promotes effective virus clearance from infected lungs when apoptosis is absent. We also demonstrate that apoptosis and necroptosis are mutually exclusive fates in IAV-infected cells. Thus, necroptosis is an independent, "stand-alone" cell death mechanism that fully compensates for the absence of apoptosis in antiviral host defense.
Asunto(s)
Caspasa 8/genética , Interacciones Microbiota-Huesped/genética , Virus de la Influenza A/inmunología , Necroptosis/genética , Infecciones por Orthomyxoviridae/inmunología , Inmunidad Adaptativa , Animales , Apoptosis/genética , Apoptosis/inmunología , Caspasa 8/metabolismo , Femenino , Técnicas de Sustitución del Gen , Interacciones Microbiota-Huesped/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Necroptosis/inmunología , Infecciones por Orthomyxoviridae/virología , Proteínas de Unión al ARN/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismoRESUMEN
Background: The animal is tremendously challenged to maintain calcium homeostasis. Those that fail can develop milk fever, a clinical disorder that is life threatening to the cow and predisposes the animal to a variety of other disorders. Calcium defi ciency disease is often accompanied with a defi ciency in phosphorus in clinical cases. Blood phosphorus status has also been researched because of the prominent interaction between calcium and phosphorus at the onset of lactation. Calcium chloride can be used to treat milk fever but it has some inadequacies such as it is soluble in water and may cause gastrointestinal irritation. To help prevent milk fever in dairy cows, we studied a calcium-phosphor-plural gel based on calcium chloride. Meanwhile, calcium chloride polymer compound added to gel, forming calcium-phosphor-plural gel, would greatly reduce the irritation. Materials, Methods & Results: Preparation of calcium-phosphor-plural gel: calcium chloride gel and calcium acid phosphate gel were mixed and grinded in a colloid burnisher (pH 7.0-7.4) and contained 21.5 mg/mL calcium and 16.4 mg/mL phosphorus. The results of the hot storage stability test, cold storage stability test, illumination test and acceleration test showed that the calcium-phosphor-plural gel did not change compared with before the tests. In safety testing, mice administered with calcium-phosphor-plural gel (less than 0.8 mL/20 g bodyweight) for 7 days did not show signs of toxicosis and pathological changes in tissues. The effect of the calcium-phosphor-plural gel on milk fever was also tested in dairy cows. The incidence rates of the calcium-phosphor-plural gel group were not signifi cantly different compared with the calcium chloride group (P > 0.05). Moreover, the calcium and phosphorus concentrations of the calcium-phosphor-plural gel group were signifi cantly higher than those in the calcium chloride group at 0, 2, 6, 24 and 72 h after calving (P < 0.05). After 72 h, the level of the phosphorus in serum in the test cows and in the control cows gradually returned to normal. The results showed that the calcium-phosphor-plural gel affected the calcium and phosphorus levels in serum and prevented milk fever in dairy cows after calving. Discussion: We used the calcium-phosphor-plural gel to prevent milk fever in dairy cows. If the calcium chloride was used to prevent milk fever in dairy cows, an intravenous injection of 5% calcium chloride after calving could increase the content of calcium in blood, and could prevent the paralysis of production due to pure hypocalcaemia. However, because of hypocalcaemia associated with hypophosphatemia, an intravenous injection of 5% calcium chloride after calving might not achieve the desired effect. To achieve a desired effect, multiple treatments may be necessary in clinical situations. This would not only increase the cost of treatment, but also increase the possibility of side effects with the use of large doses of calcium. The use of large doses of calcium would dramatically increase the concentration of calcium in blood and cause neurological disorders, or would strongly stimulate heart and cause cardiac failure or other adverse consequences, especially with rapid intravenous injection. However, the calcium- phosphor-plural gel avoids the inadequacies of calcium chloride in prevention of milk fever in dairy cows. Importantly, the calciumphosphor-plural gel could increase the content of phosphorus in the serum and adjust the balance of calcium and phosphorus in the body.
Asunto(s)
Animales , Femenino , Embarazo , Parálisis de la Parturienta/tratamiento farmacológico , Cloruro de Calcio/análisis , Fosfatos de Calcio , Enfermedades de los Bovinos , BovinosRESUMEN
Background: The animal is tremendously challenged to maintain calcium homeostasis. Those that fail can develop milk fever, a clinical disorder that is life threatening to the cow and predisposes the animal to a variety of other disorders. Calcium deficiency disease is often accompanied with a deficiency in phosphorus in clinical cases. Blood phosphorus status has also been researched because of the prominent interaction between calcium and phosphorus at the onset of lactation. Calcium chloride can be used to treat milk fever but it has some inadequacies such as it is soluble in water and may cause gastrointestinal irritation. To help prevent milk fever in dairy cows, we studied a calcium-phosphor-plural gel based on calcium chloride. Meanwhile, calcium chloride polymer compound added to gel, forming calcium-phosphor-plural gel, would greatly reduce the irritation. Materials, Methods & Results: Preparation of calcium-phosphor-plural gel: calcium chloride gel and calcium acid phosphate gel were mixed and grinded in a colloid burnisher (pH 7.0-7.4) and contained 21.5 mg/mL calcium and 16.4 mg/mL phosphorus. The results of the hot storage stability test, cold storage stability test, illumination test and acceleration test showed that the calcium-phosphor-plural gel did not change compared with before the tests. In safety testing, mice administered with calcium-phosphor-plural g
Background: The animal is tremendously challenged to maintain calcium homeostasis. Those that fail can develop milk fever, a clinical disorder that is life threatening to the cow and predisposes the animal to a variety of other disorders. Calcium deficiency disease is often accompanied with a deficiency in phosphorus in clinical cases. Blood phosphorus status has also been researched because of the prominent interaction between calcium and phosphorus at the onset of lactation. Calcium chloride can be used to treat milk fever but it has some inadequacies such as it is soluble in water and may cause gastrointestinal irritation. To help prevent milk fever in dairy cows, we studied a calcium-phosphor-plural gel based on calcium chloride. Meanwhile, calcium chloride polymer compound added to gel, forming calcium-phosphor-plural gel, would greatly reduce the irritation. Materials, Methods & Results: Preparation of calcium-phosphor-plural gel: calcium chloride gel and calcium acid phosphate gel were mixed and grinded in a colloid burnisher (pH 7.0-7.4) and contained 21.5 mg/mL calcium and 16.4 mg/mL phosphorus. The results of the hot storage stability test, cold storage stability test, illumination test and acceleration test showed that the calcium-phosphor-plural gel did not change compared with before the tests. In safety testing, mice administered with calcium-phosphor-plural g
RESUMEN
Background: The animal is tremendously challenged to maintain calcium homeostasis. Those that fail can develop milk fever, a clinical disorder that is life threatening to the cow and predisposes the animal to a variety of other disorders. Calcium deficiency disease is often accompanied with a deficiency in phosphorus in clinical cases. Blood phosphorus status has also been researched because of the prominent interaction between calcium and phosphorus at the onset of lactation. Calcium chloride can be used to treat milk fever but it has some inadequacies such as it is soluble in water and may cause gastrointestinal irritation. To help prevent milk fever in dairy cows, we studied a calcium-phosphor-plural gel based on calcium chloride. Meanwhile, calcium chloride polymer compound added to gel, forming calcium-phosphor-plural gel, would greatly reduce the irritation. Materials, Methods & Results: Preparation of calcium-phosphor-plural gel: calcium chloride gel and calcium acid phosphate gel were mixed and grinded in a colloid burnisher (pH 7.0-7.4) and contained 21.5 mg/mL calcium and 16.4 mg/mL phosphorus. The results of the hot storage stability test, cold storage stability test, illumination test and acceleration test showed that the calcium-phosphor-plural gel did not change compared with before the tests. In safety testing, mice administered with calcium-phosphor-plural g
Background: The animal is tremendously challenged to maintain calcium homeostasis. Those that fail can develop milk fever, a clinical disorder that is life threatening to the cow and predisposes the animal to a variety of other disorders. Calcium deficiency disease is often accompanied with a deficiency in phosphorus in clinical cases. Blood phosphorus status has also been researched because of the prominent interaction between calcium and phosphorus at the onset of lactation. Calcium chloride can be used to treat milk fever but it has some inadequacies such as it is soluble in water and may cause gastrointestinal irritation. To help prevent milk fever in dairy cows, we studied a calcium-phosphor-plural gel based on calcium chloride. Meanwhile, calcium chloride polymer compound added to gel, forming calcium-phosphor-plural gel, would greatly reduce the irritation. Materials, Methods & Results: Preparation of calcium-phosphor-plural gel: calcium chloride gel and calcium acid phosphate gel were mixed and grinded in a colloid burnisher (pH 7.0-7.4) and contained 21.5 mg/mL calcium and 16.4 mg/mL phosphorus. The results of the hot storage stability test, cold storage stability test, illumination test and acceleration test showed that the calcium-phosphor-plural gel did not change compared with before the tests. In safety testing, mice administered with calcium-phosphor-plural g