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The zoonotic pathogen Borrelia afzelii in its natural hosts : Bacterial dissemination and immuno-transcriptomics

Zhong, Xiuqin LU (2019)
Abstract
Most pathogens can infect a number of different host species, but host species often differ considerably in susceptibility to a given pathogen. In the case of zoonotic pathogens, natural hosts typically present little or no disease symptoms, while humans and other “spill-over” hosts often present severe symptoms. Differences in susceptibility do not only occur between natural and non-natural hosts, though, but also among natural hosts.
The natural hosts of the tick-transmitted bacterium Borrelia afzelii, which is one of three causative agents of Lyme borreliosis in humans, include a variety of small mammals like voles and mice. Studies of Borrelia infection in laboratory mice and humans have revealed mechanisms behind... (More)
Most pathogens can infect a number of different host species, but host species often differ considerably in susceptibility to a given pathogen. In the case of zoonotic pathogens, natural hosts typically present little or no disease symptoms, while humans and other “spill-over” hosts often present severe symptoms. Differences in susceptibility do not only occur between natural and non-natural hosts, though, but also among natural hosts.
The natural hosts of the tick-transmitted bacterium Borrelia afzelii, which is one of three causative agents of Lyme borreliosis in humans, include a variety of small mammals like voles and mice. Studies of Borrelia infection in laboratory mice and humans have revealed mechanisms behind susceptibility to disease. However, less is known about colonization, pathology, and host immune responses to Lyme borreliosis spirochetes in their natural hosts.
In this thesis, I used B. afzelii and its natural hosts (primarily yellow-necked mouse, Apodemus flavicollis; and bank vole, Myodes glareolus) as study system to investigate the colonization of a zoonotic pathogen in different natural host species, and the possible factors that cause inter- and intra-specific variation in susceptibility.
In papers I-III, I focused on interspecific variation in susceptibility to B. afzelii. In Paper I, I found that B. afzelii disseminates from the site of infection (skin) to internal tissues in natural hosts, like spirochetes do in non-natural hosts, but levels of colonization vary between both species and tissues. Significantly higher bacterial loads were seen in bank voles than in yellow-necked mice. However, none of the natural hosts showed signs of pathological effects of B. afzelii infection. In Paper II, species-specific regulation of immune responses (IFNα response, IL6 signaling and the complement pathway) associated with B. afzelii resistance was demonstrated by using RNA-sequencing to quantify gene expression in the spleen of voles and mice. Further analyses of the RNA-seq data set indicated that interspecific divergence in expression of pattern recognition receptors (PRRs), and cyto- and chemokines contribute disproportionately to interspecific variation in immune function in general (Paper III). In Paper IV, I focused on intra- specific variation in resistance in the bank vole, and showed that the previously demonstrated effect of variation in the PRR TLR2 on resistance to B. afzelii could be a result of polymorphisms in the coding sequence, and/or polymorphisms in non-coding sequences affecting expression of TLR2.
In summary, the findings in this study have provided new insights to understand the causes of inter- and intraspecific variation in susceptibility to a zoonotic pathogen in its natural host species. (Less)
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author
supervisor
opponent
  • Associate Professor Vinkler, Michal, Charles University, Prague, Czech Republic
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Borrelia afzelii, natural hosts, bacterial load, immune response, RNA-seq
pages
53 pages
publisher
Lund University
defense location
Biologihörsalen A213, The Biology Building, Sölvegatan 35, Lund
defense date
2020-01-17 09:00:00
ISBN
978-91-7895-371-4
978-91-7895-370-7
project
Borrelia in rodents
language
English
LU publication?
yes
id
07ced3e4-2ebc-4027-b6dd-27143f2c82ce
date added to LUP
2019-12-02 16:33:54
date last changed
2019-12-12 15:57:10
@phdthesis{07ced3e4-2ebc-4027-b6dd-27143f2c82ce,
  abstract     = {Most pathogens can infect a number of different host species, but host species often differ considerably in susceptibility to a given pathogen. In the case of zoonotic pathogens, natural hosts typically present little or no disease symptoms, while humans and other “spill-over” hosts often present severe symptoms. Differences in susceptibility do not only occur between natural and non-natural hosts, though, but also among natural hosts.<br/>The natural hosts of the tick-transmitted bacterium <i>Borrelia afzelii</i>, which is one of three causative agents of Lyme borreliosis in humans, include a variety of small mammals like voles and mice. Studies of <i>Borrelia</i> infection in laboratory mice and humans have revealed mechanisms behind susceptibility to disease. However, less is known about colonization, pathology, and host immune responses to Lyme borreliosis spirochetes in their natural hosts.<br/>In this thesis, I used <i>B. afzelii</i> and its natural hosts (primarily yellow-necked mouse, <i>Apodemus flavicollis</i>; and bank vole, <i>Myodes glareolus</i>) as study system to investigate the colonization of a zoonotic pathogen in different natural host species, and the possible factors that cause inter- and intra-specific variation in susceptibility.<br/>In papers I-III, I focused on interspecific variation in susceptibility to <i>B. afzelii</i>. In <b>Paper I</b>, I found that <i>B. afzelii</i> disseminates from the site of infection (skin) to internal tissues in natural hosts, like spirochetes do in non-natural hosts, but levels of colonization vary between both species and tissues. Significantly higher bacterial loads were seen in bank voles than in yellow-necked mice. However, none of the natural hosts showed signs of pathological effects of B. afzelii infection. In <b>Paper II</b>, species-specific regulation of immune responses (IFNα response, IL6 signaling and the complement pathway) associated with <i>B. afzelii</i> resistance was demonstrated by using RNA-sequencing to quantify gene expression in the spleen of voles and mice. Further analyses of the RNA-seq data set indicated that interspecific divergence in expression of pattern recognition receptors (PRRs), and cyto- and chemokines contribute disproportionately to interspecific variation in immune function in general (<b>Paper III</b>). In <b>Paper IV</b>, I focused on intra- specific variation in resistance in the bank vole, and showed that the previously demonstrated effect of variation in the PRR <i>TLR2</i> on resistance to <i>B. afzelii</i> could be a result of polymorphisms in the coding sequence, and/or polymorphisms in non-coding sequences affecting expression of <i>TLR2</i>.<br/>In summary, the findings in this study have provided new insights to understand the causes of inter- and intraspecific variation in susceptibility to a zoonotic pathogen in its natural host species.},
  author       = {Zhong, Xiuqin},
  isbn         = {978-91-7895-371-4},
  language     = {eng},
  month        = {12},
  publisher    = {Lund University},
  school       = {Lund University},
  title        = {The zoonotic pathogen Borrelia afzelii in its natural hosts : Bacterial dissemination and immuno-transcriptomics},
  url          = {https://lup.lub.lu.se/search/ws/files/72669547/Xiuqin_Zhong_web.pdf},
  year         = {2019},
}