Abstract
Malaria is a significant world health problem, with billions of people at risk and over 200 million clinical cases per year that result in over 200,000 deaths. However, the majority of the population in malaria endemic areas (>60%) is asymptomatic (without overt symptoms), even in high transmission areas. Although identified by Plasmodium-infected red blood cells in the circulation, the term asymptomatic malaria is a misnomer with individuals experiencing mild anemia, vascular activation and increased susceptibility to co-morbidities such as non-typhoidal Salmonella infections. The immunological mechanisms governing the development and maintenance of asymptomatic malaria are poorly understood and the influence of host genetics in endemic populations is unknown. Currently, no immunologically intact animal model is available to understand how host genetics influence the asymptomatic nature of Plasmodium infection. Here, we use wild-derived Mus musculus to show that the genetic diversity seen in the wild host population leads to increased variation in anemia upon infection with Plasmodium yoelii XNL with a subpopulation of mice experiencing asymptomatic malaria with mild anemia. Plasma TNF-a was positively correlated with the level of anemia, as might be expected from studies showing a positive correlation of TNF-a with anemia in children. Also, there was a negative correlation between monocyte populations and anemia experienced by the mice, which has also been observed in asymptomatic children in eastern Uganda. These results show that the wild derived mice can model asymptomatic malaria and allow us to interrogate the different immune profiles that lead to the range of phenotypes to malarial disease.
