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 or endothelial sites. NTS is an intestinal pathogen, however the contribution of bacterial translocation from the intestinal tract during Plasmodium infection is not well studied. Here, we investigated the integrity of the intestinal barrier function of P. chabaudi-infected mice using large molecules and Salmonella infection. 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 malaria-specific immune responses by bacteremia. These studies demonstrate that P. chabaudi infection induces failure of the barrier function of the intestinal wall and enhanced intestinal bacterial translocation, affecting anti-malarial immunity.
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Acknowledgments
We would like to thank Mark Griffin in the Department of Microbiology and Immunology Flow Cytometry and Cell Sorting Core Facility for his kind assistance. In addition, we appreciate the members of the Chopra lab for generous experimental help.
Funding
Funding was provided by UTMB Department of Internal Medicine, Division of Infectious Diseases, NIH (R01AI089953 (RS)) and the Saudi Arabian Cultural Mission, Jazan University.
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards and protocols approved by the University of Texas Medical Branch Institutional Animal Care and Use Committee.
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Alamer, E., Carpio, V.H., Ibitokou, S.A. et al. Dissemination of non-typhoidal Salmonella during Plasmodium chabaudi infection affects anti-malarial immunity. Parasitol Res 118, 2277–2285 (2019). https://doi.org/10.1007/s00436-019-06349-z
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DOI: https://doi.org/10.1007/s00436-019-06349-z