Abstract

In the Plasmodium infected host, a balance between pro- and anti-inflammatory responses is required to clear the parasites without inducing major host pathology. Clinical reports suggest that bacterial infection in conjunction with malaria aggravates disease and raises both mortality and morbidity in these patients. In this study, we investigated the immune responses in BALB/c mice, co-infected with Plasmodium berghei NK65 parasites and the relapsing fever bacterium Borrelia duttonii. In contrast to single infections, we identified in the co-infected mice a reduction of L-Arginine levels in the serum. It indicated diminished bioavailability of NO, which argued for a dysfunctional endothelium. Consistent with this, we observed increased sequestration of CD8+ cells in the brain as well over expression of ICAM-1 and VCAM by brain endothelial cells. Co-infected mice further showed an increased inflammatory response through IL-1 beta and TNF-alpha, as well as inability to down regulate the same through IL-10. In addition we found loss of synchronicity of pro- and anti-inflammatory signals seen in dendritic cells and macrophages, as well as increased numbers of regulatory T-cells. Our study shows that a situation mimicking experimental cerebral malaria (ECM) is induced in co-infected mice due to loss of timing and control over regulatory mechanisms in antigen presenting cells.

Published in

PLoS ONE
2014, Volume: 9, number: 7, article number: e103295
Publisher: PUBLIC LIBRARY SCIENCE

SLU Authors

• Moritz, Thomas

  • Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences
    

Sustainable Development Goals

SDG3 Ensure healthy lives and promote well-being for all at all ages


UKÄ Subject classification

Biochemistry and Molecular Biology
Microbiology in the medical area


Publication identifier

DOI: https://doi.org/10.1371/journal.pone.0103295

Permanent link to this page (URI)

https://res.slu.se/id/publ/67591