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Enhanced inflammatory response to relapsing fever during pregnancy
Umeå universitet, Medicinsk fakultet, Molekylärbiologi (Medicinska fakulteten).
Vise andre og tillknytning
Manuskript (Annet vitenskapelig)
Identifikatorer
URN: urn:nbn:se:umu:diva-3749OAI: oai:DiVA.org:umu-3749DiVA, id: diva2:142594
Tilgjengelig fra: 2009-01-21 Laget: 2009-01-21 Sist oppdatert: 2010-01-13bibliografisk kontrollert
Inngår i avhandling
1. Immunopathogenesis of relapsing fever borreliosis
Åpne denne publikasjonen i ny fane eller vindu >>Immunopathogenesis of relapsing fever borreliosis
2008 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Relapsing fever (RF) is caused by different species of Borrelia transmitted by soft ticks or by the human body louse. Illness is characterized by reappearing peaks of high concentrations of spirochetes in blood, concordant with fever peaks separated by asymptomatic periods. Neuroborreliosis is one of the most severe manifestations of RF borreliosis. To understand the immune response during early RF, we analyzed immune cells in brain and kidney of mice infected with B. crocidurae during the acute infection. Our results indicate that brain defense is comprised primarily of innate immune cells. Despite the infiltration of innate immune cells, Borrelia was not completely eradicated. A failure of the host brain to clear the bacteria may give the pathogen a niche where it can persist. Using our mouse model, we revealed that Borrelia duttonii could persist in the mouse brain for up to 270 days, without being present in the circulation. The infection was silent with no change in host gene expression, and the spirochetes could re-enter the circulation after immunosuppression. We propose that the brain is used by the pathogen to evade host immunity and serves as a possible natural reservoir for B. duttonii, a spirochete that has rarely been found in any mammalian host other than man. Borrelia-induced complications during pregnancy have been reported, and are especially common in RF. In our established mouse model of gestational RF, we could show that the fetuses suffered from severe pathology and growth retardation, probably as a consequence of placental destruction. We could also show trans-placental transmission of the bacteria leading to neonatal RF. Surprisingly, pregnant dams had a lower bacterial load and less severe disease, showing that pregnancy has a protective effect during RF. We have used the gestational RF model to investigate host factors favoring disease resolution. Because the spleen is the primary organ responsible for trapping and removing blood-borne pathogens, we have compared temporal changes in spleen immune cell populations and cytokine/chemokine induction during the infection. Spleens of pregnant mice had earlier neutrophil infiltration, as well as faster and higher production of pro-inflammatory mediators. This rapid, robust response suggests a more effective host defense. Thus, an enhanced pro-inflammatory response during pregnancy imparts a distinct advantage in controlling the severity of relapsing fever infection.

sted, utgiver, år, opplag, sider
Umeå: Molekylärbiologi (Medicinska fakulteten), 2008. s. 102
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1236
Emneord
Relapsing fever, Borrelia, mouse models, biological barriers, pathology, chemokines, cytokines, pregnancy
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-1968 (URN)978-91-7264-710-7 (ISBN)
Disputas
2009-01-16, Major Groove, Byggnad 6L, Institutionen för Molekylärbiologi, Umeå Universitet, Umeå, 09:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2009-01-21 Laget: 2009-01-21 Sist oppdatert: 2018-06-09bibliografisk kontrollert

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