Abstract
Malaria-associated bacteremia accounts for up to one third of deaths from severe malaria, and non-typhoidal
Salmonella
(NTS) has been reported as a major complication of severe malarial infection. Patients who develop NTS bacteremia during
Plasmodium
infection show higher mortality rates than individuals with malaria alone. Systemic bacteremia can be caused by a wound or translocation from epithelial sites. Although NTS is an intestinal pathogen, the contribution of bacterial translocation from the intestinal tract during
Plasmodium
infection is not well studied. Here, we investigated the integrity of intestinal barrier function of
P. chabaudi-
infected mice using large molecules and the intestinal pathogen,
Salmonella
. Intestinal histology and the adaptive immune response to malaria were also studied using light microscopy and flow cytometry.
P. chabaudi
infection compromised intestinal barrier function, which led to increased intestinal cellular infiltration. In addition, we observed increased serum lipopolysaccharide binding protein and leakage of soluble molecules from the intestine into the blood in infected mice.
Plasmodium
infection also increased intestinal translocation and dissemination of NTS to the liver. The adaptive immune response to
P. chabaudi
infection was also significantly impacted by NTS translocation. Reduced B and T cell activation were observed in co-infected animals, suggesting interference in the malarial-specific immune responses by bacteremia. These studies demonstrate that
P. chabaudi
infection induces a failure of the barrier function of the intestinal wall and enhanced intestinal bacterial translocation, affecting anti-malarial immunity.