Genetic growth potential interacts with nutrition on the ability of mice to cope with Heligmosomoides bakeri infection.

Artificial selection for improved productivity may reduce an animal's ability to cope with pathogens. Here, we used Roslin mice, uniquely divergently selected for high (ROH) and low (ROL) body weight, to assess interactive effects of differing growth potential and protein nutrition on host resilience and resistance. In a 2 x 2 x 6 factorial design, ROH and ROL mice were either sham-infected or infected with 250 L(3)Heligmosomoides bakeri and fed diets with 30, 80, 130, 180, 230 and 280 g crude protein per kg. The infected ROL-30 treatment resulted in clinical disease and was discontinued. In the remaining ROL mice, infection and feeding treatments did not affect growth but infection reduced weight gain in ROH-30, ROH-80 and ROH-130 mice. Although infection resulted in temporarily reduced food intake (anorexia) in both mouse lines, mean food intake over the whole experiment was reduced in ROH mice only. ROH mice excreted more worm eggs and had higher worm burdens, with relatively fewer female worms, than ROL mice. However, these resistance traits were not sensitive to dietary protein. These results support the view that selection for high growth may reduce the ability to cope with pathogens, and that improved protein nutrition may to some extent ameliorate this penalty.

The parasitic worm-derived immunomodulator, ES-62 and its drug-like small molecule analogues exhibit therapeutic potential in a model of chronic asthma.

Chronic asthma is associated with persistent lung inflammation and long-term remodelling of the airways that have proved refractory to conventional treatments such as steroids, despite their efficacy in controlling acute airway contraction and bronchial inflammation. As its recent dramatic increase in industrialised countries has not been mirrored in developing regions, it has been suggested that helminth infection may protect humans against developing asthma. Consistent with this, ES-62, an immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, can prevent pathology associated with chronic asthma (cellular infiltration of the lungs, particularly neutrophils and mast cells, mucus hyper-production and airway thickening) in an experimental mouse model. Importantly, ES-62 can act even after airway remodelling has been established, arresting pathogenesis and ameliorating the inflammatory flares resulting from repeated exposure to allergen that are a debilitating feature of severe chronic asthma. Moreover, two chemical analogues of ES-62, 11a and 12b mimic its therapeutic actions in restoring levels of regulatory B cells and suppressing neutrophil and mast cell responses. These studies therefore provide a platform for developing ES-62-based drugs, with compounds 11a and 12b representing the first step in the development of a novel class of drugs to combat the hitherto intractable disorder of chronic asthma.