Nutritional regulation of resistance to Nippostrongylus brasiliensis in the lactating rat

Animals acquire immunity against gastrointestinal (GI) nematode infection depending on their age and continual exposure to larvae, however, expression of this acquired immunity is often penalized during pregnancy and lactating period. This is described as periparturient relaxation in immunity (PPRI), and suggested to have nutritional basis. Although dietary protein has positive effect on immunity against GI nematode infection in mammalian host, we have not fully achieved to characterise the detailed interaction between PPRI and dietary protein. Therefore, this PhD aimed to further investigate this interaction in a well-established Nippostrongylus brasiliensis re-infected lactating rat model. Feeding high protein diet (HP) as opposed to low protein diet (LP) during pregnancy was necessary in maintaining sufficient maternal performances and systemic immune response (Chapter 2 and 3). Accumulation of host’s body protein reserve during pregnancy was significantly higher in HP fed animals compared to LP fed counterparts, which led to improvement in both maternal performances and immunity during the early stage of lactation. However, as lactation period progressed and re-infection of N. brasiliensis took place, importance of current dietary status, rather than the accumulated protein reserve, became evident for maternal performances and immunity. Indeed, animals fed HP during lactation showed significantly heavier pup weight compared to LP fed animals; HP animals showed higher serum immunoglobulin levels and reduced worm burden compared to LP. N. brasiliensis, however, goes through systemic migration, entering host’s skin and migrating to lung parenchyma through blood vessels before reaching the intestine. In Chapter 4, a detailed lung pathology study following N. brasiliensis infection was performed to generate data on the effects of the nematode in the lung of the rat host as such data were scarce. Rat host showed similar lung pathology to that of mice; up-regulation of genes related to type 2 immunity and development of emphysema-like pathology were observed following N. brasiliensis re-infection. In Chapter 5, the effect of dietary protein supplementation on lung and intestinal histology and gene expression analysis was investigated. It was shown that HP fed animals showed higher expression of genes related to type 2 immunity compared to LP in the lung. This effect of protein supplementation in the lung may have contributed to fewer worm burdens in HP fed rats compared to LP in the intestine. Dietary protein supplementation significantly affected the expression of genes related to goblet cells; it resulted in up-regulation of the expression of Retnlb and down-regulation of Agr2 and Tff3 in HP fed animals compared to LP. It is evident that dietary protein is modulating intestinal immunity, and this may be targeted towards specific pathways. In addition, the effect of dietary protein supplementation on immune cell populations of secondary lymphoid organs was analysed. Marked increase in the percentage of macrophage in the spleen and T cell in the mesenteric lymph node was observed following protein supplementation, highlighting the importance of dietary protein on systemic immunity during the parasite infection. These results demonstrate that dietary protein supplementation is effective for improving both maternal performances and immune responses, not only at the intestinal phase but also at the migrating phase, when animal is undergoing PPRI during N. brasiliensis infection. Such information is expected to define strategic utilisation of nutrient supply and to result in development of sustainable parasite control strategies in mammals