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Doctoral thesis, 1999

Host interactions of the intracellular bacterium Coxiella burnetii : internalisation, induction of bacterial proteins and host response upon infection

Tujulin, Eva

Abstract

Q fever is a zoonosis caused by the obligate intracellular bacterium Coxiella burnetii. The aim of this thesis was to study internalisation of C. burnetii, the induction of bacterial proteins upon infection, and the initial host response to C. burnetii infection. A comparison of host response after infection with virulent and avirulent C. burnetii was made.

C. burnetii infects a variety of cells, including macrophages. Previously, C. burnetii has been reported to enter host cells passively via phagocytosis. To further examine the mechanism of C. burnetii internalisation, macrophage monolayers were treated with well known inhibitors of endocytosis. The results indicate that C. burnetii may utilise both pinocytosis and phagocytosis for internalisation.

C. burnetii proliferates within the acidic phagolysosome of eukaryotic cells. To study proteins induced dining phagolysosome-like conditions bacteria were incubated in an acidic in vitro system. One o f these proteins was identified as an Hsp70 homologue. The C. burnetii Hsp71 -kDa protein is one of the predominant proteins induced early in acid activated bacteria.

In intracellular infection, macrophages have been shown to secrete cytokines that are capable of modulating the cellular immune response. To study early host response in vitro, macrophages were infected with virulent and avirulent C. burnetii. We found that virulence of the bacteria, seems to be correlated to an enhancement of IL -la production during the initial hours of infection.

To further characterize the host response an in vivo model in mice was used. Mice infected with virulent C. burnetii appeared depressed and grossly splenomegaly was observed. In lungs of these mice histological lesions appeared earlier and did not resolve as soon as in infection with avirulent bacteria. Typical changes in lung consisted o f interstitial inflammatory reactions, with infiltration of mononuclear cells. In liver multifocal granulomas were observed, the frequency of granulomas was considerably higher in mice infected by virulent C. burnetii.

Cytokine mRNAs were analysed in lung. An obvious induction of IL-lp mRNA was observed in lungs o f mice infected with virulent C. burnetii during the acute phase of infection. The results from the in vitro and in vivo infection model indicates that the innate immune response in virulent C. burnetii infection is correlated to an early induction of IL-1.

Keywords

Q fever; Coxiella burnetii; internalisation; endocytosis; heat shock proteins; Hsp70 homologue; cytokines; macrophage; LPS; IL-1; mouse infection model.

Published in

Acta Universitatis Agriculturae Sueciae. Veterinaria
1999, number: 52
ISBN: 91-576-5425-5
Publisher: Swedish University of Agricultural Sciences

Authors' information

Tujulin, Eva
Swedish University of Agricultural Sciences, Department of Pathology

UKÄ Subject classification

Pathobiology

URI (permanent link to this page)

https://res.slu.se/id/publ/117455