Current vaccines to Escherichia coli mastitis have shown some albeit limited efficacy. Their mode of action has not been documented, and immune responses protecting the mammary gland against E. coli are not completely understood. To improve our knowledge of mammary gland immune protection, cows immunized either intramuscularly or intramammarily with the E. coli P4 were submitted to a homologous mastitis challenge. A third group of mock-immunized cows serve as challenge controls. Local immunization modified favorably the course of infection, by improving bacterial clearance while limiting inflammation. Systemic clinical signs and reduction in milk secretion were also contained. This occurred with a modification of the cytokine profile, such as an increase in IFN-γ and a reduction in TNF-α concentrations in milk. Concentrations of IL-17A and IL-22 increased in milk at the onset of the inflammatory response and remained high up to the elimination of bacteria, but concentrations did not differ between groups. Accelerated bacteriological cure was not linked to an increase in the initial efficiency of phagocytosis in milk. Results support the idea that antibodies did not play a major role in the improvement, and that cell-mediated immunity is the key to understanding E. coli vaccine-induced protection of the mammary gland.
The pineal gland secretes melatonin (MLT) that circulates in the blood and cerebrospinal fluid (CSF). We provide data to support the hypothesis that, in sheep and possibly in humans, only the CSF MLT, and not the blood MLT, can provide most of MLT to the cerebral tissue in high concentrations, particularly in the periventricular area. The MLT content of sheep brain, our chosen animal model, was found in significant concentration gradients oriented from the ventricle (close to the CSF) to the cerebral tissue, with concentrations varying by a factor of 1-125. The highest concentrations were observed close to the ventricle wall, whereas the lowest concentrations were furthest from the ventricles (407.0 ± 71.5 pg/ml compared to 84.7 ± 5.2 pg/ml around the third ventricle). This concentration gradient was measured in brain tissue collected at mid-day and at the end of the night. Nocturnal concentrations were higher than daytime concentrations, reflecting the diurnal variation in the pineal gland. The concentration gradient was not detected when MLT was delivered to the brain via the bloodstream. The diffusion of MLT to cerebral tissues via CSF was supported by in vivo scintigraphy and autoradiography. 2-[(123)I]-MLT infused into the CSF quickly and efficiently diffused into the brain tissues, whereas [(123)I]-iodine (control) was mostly washed away by the CSF flow and [(123)I]-bovine serum albumin remained mostly in the CSF. Taken together, these data support a critical role of CSF in providing the brain with MLT.
Oral contamination with bovine spongiform encephalopathy (BSE) agent in susceptible PRNP genotype sheep results in widespread distribution of prion in the host. Because ARR homozygous sheep are considered to be resistant to transmissible spongiform encephalopathies, they have been selected to eradicate scrapie from sheep flocks and to protect the human food chain from small ruminant BSE risk. However, results presented here show that several months after an oral challenge with BSE agent, healthy ARR/ARR sheep can accumulate significant amounts of PrP Sc in the spleen.
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