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Maladjusted Host Immune Responses Induce Experimental Cerebral Malaria-Like Pathology in a Murine Borrelia and Plasmodium Co-Infection Model

Normark, Johan (author)
Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för klinisk mikrobiologi
Nelson, Maria (author)
Umeå universitet,Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
Engström, Patrik, 1982- (author)
Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Umeå Centre for Microbial Research (UCMR),Molekylär Infektionsmedicin, Sverige (MIMS),Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America
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Andersson, Marie (author)
Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten)
Björk, Rafael (author)
Umeå universitet,Institutionen för matematik och matematisk statistik
Moritz, Thomas (author)
Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för skoglig genetik och växtfysiologi,Department of Forest Genetics and Plant Physiology
Fahlgren, Anna (author)
Umeå universitet,Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
Bergström, Sven (author)
Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
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 (creator_code:org_t)
 
2014-07-30
2014
English.
In: PLOS ONE. - : PLOS ONE. - 1932-6203. ; 9:7
Related links:
https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
https://journals.plo...
https://urn.kb.se/re...
https://doi.org/10.1...
https://res.slu.se/i...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

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