Nutritional sensitivity of periparturient breakdown of immunity to gastrointestinal nematode parasites in mammals

Mammals usually develop immunity to gastrointestinal nematode parasites. However, during late pregnancy and lactation, this immunity often breaks down, resulting in elevated levels of parasitism. This periparturient relaxation of immunity (PPRI) renders lactating hosts main sources of infection for their parasite-naïve offspring, and may have a nutritional basis. Results of studies on parasitized hosts suggest that both crude protein (CP) and metabolizable energy (ME) supply may be important in regulating the degree of PPRI by affecting the immune response towards parasites. However there is a scarcity of data supporting such a role for ME in periparturient hosts, while there is sufficient evidence to support the view that CP in general, and amino acids are potent immunonutrients in various disease states (Chapter 1). In the first experiment (Chapter 2) I seperated effects of CP and ME on PPRI by feeding parasitized lactating rats at two levels of ME supply and one of three levels of CP supply. The results show that PPRI is sensitive to CP scarcity, and not to moderate ME scarcity. Increasing CP supply improved lactational performance and reduced PPRI, as observed by reduced worm burdens. In the second experiment (Chapter 3) I examined the rate at which improved nutrition can restore immunity by feeding low protein diets to rats nursing high number of pups, and then reduced litter size in a sub-group so that host nutritional status would change from scarce to adequate. The egg production of the parasite population of the latter group reduced within days to similarly low levels as rats that had always reared low number of pups and this was associated with an increased number of musosal mast cells and increased dam weight gain. Since host responses to dietary CP are almost by ii definition responses to essential amino acids, the third experiment assessed the sensitivity of PPRI to methionine and leucine deficiency (Chapter 4). The latter resulted in increased worm burdens and egg production to similar levels when low protein diets are fed and imposed penalties in lactational performance. Finally, in the fourth experiment it was investigated whether similar outcomes can be expected in periparturient ruminant hosts by supplementing sheep with field beans, which are deficient in methionine, instead of soybean meal (Chapter 5). Indeed, feeding high protein diets based on field beans was less effective in reducing the worm egg excretion and improving lactational performance. The data from this thesis (Chapter 6) provide novel information on the nutritional basis of PPRI, showing that the latter can be rapidly reduced through improved protein nutrition. This may be seen as a response to the protein quality of the diet and the supply of amino acids in optimum quantities. These results have implications for parasite control strategies in farm animals

A Four-Biomarker Blood Signature Discriminates Systemic Inflammation Due to Viral Infection Versus Other Etiologies

The innate immune system of humans and other mammals responds to pathogen-associated molecular patterns (PAMPs) that are conserved across broad classes of infectious agents such as bacteria and viruses. We hypothesized that a blood-based transcriptional signature could be discovered indicating a host systemic response to viral infection. Previous work identified host transcriptional signatures to individual viruses including influenza, respiratory syncytial virus and dengue, but the generality of these signatures across all viral infection types has not been established. Based on 44 publicly available datasets and two clinical studies of our own design, we discovered and validated a four-gene expression signature in whole blood, indicative of a general host systemic response to many types of viral infection. The signature's genes are: Interferon Stimulated Gene 15 (ISG15), Interleukin 16 (IL16), 2',5'-Oligoadenylate Synthetase Like (OASL), and Adhesion G Protein Coupled Receptor E5 (ADGRE5). In each of 13 validation datasets encompassing human, macaque, chimpanzee, pig, mouse, rat and all seven Baltimore virus classification groups, the signature provides statistically significant (p < 0.05) discrimination between viral and non-viral conditions. The signature may have clinical utility for differentiating host systemic inflammation (SI) due to viral versus bacterial or non-infectious causes