Moderate Malnutrition exacerbates Plasmodium chabaudi induced gut leakage and reduced mucosal Innate Immunity in mice

Abstract

Abstract Gastrointestinal problems are among the most reported symptoms in serious cases of malaria infection. While many pathophysiologies including gastric mucosal changes have been reported in serious cases of malaria infection, the influence of moderate malnutrition, common in malaria endemic areas, has not been well explored. Here, we used a rodent mouse model to investigate how moderate malnutrition affects gut integrity and mucosal innate immunity during malaria. Utilizing a well-established low protein diet that is deficient in zinc and iron to induce moderate malnutrition, we investigated mucosal tissue phenotype and integrity, and mucosal innate immunity in the gut. We observed that the infected moderate malnourished mice had lower parasite burden at the peak of infection, but high levels of FITC-Dextran concentration in the blood serum, indicating increased intestinal permeability. The small intestines in the moderate malnourished mice were also shorter after infection with malaria. This was accompanied with lower numbers of CD11b+macrophages, CD11b+CD11c+ myeloid cells, and CD11c+ dendritic cells in the small and large intestines. Despite the lower number of innate immune cells, macrophages in the malnourished mice were highly activated as determined by MHCII expression. Thus, our data suggests that malaria infection may exacerbate the deformities in the gut induced by moderate malnutrition.