Plasmodium chabaudi Infection Alters Intestinal Morphology and Mucosal Innate Immunity in Moderately Malnourished Mice

Nutrients. 2021 Mar 11;13(3):913. doi: 10.3390/nu13030913.

Abstract

Plasmodium falciparum is a protozoan parasite which causes malarial disease in humans. Infections commonly occur in sub-Saharan Africa, a region with high rates of inadequate nutrient consumption resulting in malnutrition. The complex relationship between malaria and malnutrition and their effects on gut immunity and physiology are poorly understood. Here, we investigated the effect of malaria infection in the guts of moderately malnourished mice. We utilized a well-established low protein diet that is deficient in zinc and iron to induce moderate malnutrition and investigated mucosal tissue phenotype, permeability, and innate immune response in the gut. We observed that the infected moderately malnourished mice had lower parasite burden at the peak of infection, but damaged mucosal epithelial cells and high levels of FITC-Dextran concentration in the blood serum, indicating increased intestinal permeability. The small intestine in the moderately 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 large intestine. Despite the lower number of innate immune cells, macrophages in the moderately malnourished mice were highly activated as determined by MHCII expression and increased IFNγ production in the small intestine. Thus, our data suggest that malaria infection may exacerbate some of the abnormalities in the gut induced by moderate malnutrition.

Keywords: gut immunity; innate immunity; intestinal permeability; malaria; malnutrition.

MeSH terms

  • Animals
  • Cytokines / biosynthesis
  • Immunity, Innate*
  • Immunity, Mucosal*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology*
  • Intestine, Large / immunology
  • Intestine, Large / pathology
  • Intestine, Small / immunology
  • Intestine, Small / pathology
  • Macrophages / immunology
  • Malaria / complications*
  • Malaria / immunology
  • Malaria / pathology
  • Male
  • Malnutrition / complications*
  • Malnutrition / immunology
  • Malnutrition / pathology
  • Mice
  • Mice, Inbred C57BL
  • Plasmodium chabaudi*

Substances

  • Cytokines