Change search
ReferencesLink to record
Permanent link

Direct link
Malaria-enhanced Neutrophil Dependent Clearance of S. pneumoniae in an in vivo Co-infection Model
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Show others and affiliations
(English)Manuscript (preprint) (Other (popular science, discussion, etc.))
National Category
Cell and Molecular Biology
URN: urn:nbn:se:umu:diva-102818OAI: diva2:809960

Orifinally published with the title: Malaria-induced alteration of neutrophils to clear S. pneumoniae in vivo

Available from: 2015-05-05 Created: 2015-05-05 Last updated: 2015-05-06
In thesis
1. Host responses to malaria and bacterial co-­infections
Open this publication in new window or tab >>Host responses to malaria and bacterial co-­infections
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The two main causes of child mortality and morbidity in Africa are malaria and invasive bacterial diseases. In addition, co-infections in sub-Saharan Africa are the rule rather than the exception. However, not much is known about the host-pathogen interaction during a concomitant infection or how it affects the outcome of disease.

In order to study the immunological responses during malaria and bacterial co-infections, we established a co-infection mouse model. In these studies we used two pathogenic bacteria found in malaria co-infected patients: Streptococcus pneumoniae and Relapsing fever Borrelia duttonii.

Hosts co-infected with malaria and Borrelia showed greatly increased spirochetal growth but low parasite densities. In addition, the co-infected hosts presented symptoms of experimental-cerebral malaria, in an otherwise unsusceptible mouse model. This was found to be a consequence of a dysregulated immune response due to loss of timing and control over regulatory mechanisms in antigen presenting cells thus locking the host in an inflammatory response. This results in inflammation, severe anemia, internal organ damage and pathology of experimental cerebral malaria.

On the other hand, in the malaria - S. pneumoniae co-infection model we found that co-infected hosts cleared the bacterium much more efficiently than the single infected counterpart. This efficiency of clearance showed to be neutrophil dependent. Furthermore, in vitro studies revealed that neutrophils isolated from malaria-infected hosts present an altered migratory effect together with a significantly increased capacity to kill S. pneumoniae. This suggests that a malaria infection primes neutrophils to kill S. pneumoniae more efficiently.

Furthermore, a study was carried out on plasma samples from Rwandan children under the age of five, on which a full metabolomics profile was performed. We showed that these children could be divided in different disease categories based on their metabolomics profile and independent of clinical information. Additionally, the mild malaria group could further be divided in two sub-groups, in which one had a metabolomic profile resembling that of severe malaria infected patients. Based on this, metabolite profiling could be used as a diagnostic tool to determine the distinct phase, or severity of a malaria infection, identify risk patients and provide helpful and correct therapy. 

Place, publisher, year, edition, pages
Umeå Universitet: Umeå universitet, 2015. 59 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1720
Plasmodium, Malaria, Borrelia, S. pneumoniae, Co-infection, Immunology, Metabolomics
National Category
Cell and Molecular Biology
urn:nbn:se:umu:diva-102795 (URN)978-91-7601-276-5 (ISBN)
Public defence
2015-05-29, Major Grove, Building J1, Department of Molecular Biology, Umeå, 09:00 (English)
Available from: 2015-05-08 Created: 2015-05-05 Last updated: 2015-05-08Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Nelson, MariaNiemic, Maria JoannaFahlgren, AnnaUrban, ConstantinNormark, JohanBergström, Sven
By organisation
Department of Molecular Biology (Faculty of Medicine)Department of Clinical MicrobiologyMolecular Infection Medicine Sweden (MIMS)Umeå Centre for Microbial Research (UCMR)
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 142 hits
ReferencesLink to record
Permanent link

Direct link