Abstract
Enteric infectious diseases are not all well controlled, which leads to animal suffering and sometimes death in the most severe cases, in addition to economic losses for farmers. Typical symptoms of enteric infections include watery diarrhea, stomach cramps or pain, dehydration, nausea, vomiting, fever and weight loss. Evaluation of new control methods against enteric infections requires the use of many animals. We aimed to develop a new method for an initial in vivo screen of promising compounds against neonatal diseases such as cryptosporidiosis while limiting experimental animal use. We therefore adapted an in vivo method of multiple consecutive but independent intestinal loops to newborn lambs delivered by cesarean section, in which endotoxin responsiveness is retained. This new method allowed for the screening of natural yeast fractions for their ability to stimulate immune responses and to limit early Cryptosporidium parvum development. This model may also be used to investigate host–pathogen interactions and immune responses in a neonatal controlled environment.
Highlights
Infectious diseases are mainly controlled by the use of vaccines and antimicrobials.Despite major discoveries, some infectious diseases remained refractory to vaccination and treatments and require specific attention together with the new infectious zoonotic threats that increasingly emerge these last decades
Food intake was slightly lower in gut-loop lambs, but all animals were regularly fed on several occasions during the first 24 h (Figure 1e)
We aim to stimulate the immune responses of animals from birth with colostrum supplemented with natural products and in particular yeast cell wall (YCW) fractions that contain TLR2 and TLR4 ligands
Summary
Infectious diseases are mainly controlled by the use of vaccines and antimicrobials.Despite major discoveries, some infectious diseases remained refractory to vaccination and treatments and require specific attention together with the new infectious zoonotic threats that increasingly emerge these last decades. The evaluation of new antimicrobials is usually first performed by bioinformatics and/or by in vitro approaches sometimes resulting from High-Throughput Screening (HTS) on miniaturized 2D cell-based assays, evaluating 100,000 or more samples per day [1,2] Many of these candidates failed when entering clinical trials and have required the unnecessary use of numerous experimental animals. Ex vivo cultures of multipotent or pluripotent stem cells in a three-dimensional (3D) matrix represent major improvements and contribute to reducing animal use [3,4] Despite their obvious advantages, these systems cannot yet fully reproduce all the complex characteristics and interactions encountered in vivo, such as the (I) multiplicity and spatial organization of cell types, (II) the immune cell recruitments, (III) the ability to
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