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- Title
Atg5-Deficient Mice Infected with Francisella tularensis LVS Demonstrate Increased Survival and Less Severe Pathology in Internal Organs.
- Authors
Kelava, Ina; Mihelčić, Mirna; Ožanič, Mateja; Marečić, Valentina; Knežević, Maša; Ćurlin, Marija; Štifter, Sanja; Sjöstedt, Anders; Šantić, Marina
- Abstract
Francisella tularensis is a highly virulent intracellular pathogen that proliferates within various cell types and can infect a multitude of animal species. Francisella escapes the phagosome rapidly after infection and reaches the host cell cytosol where bacteria undergo extensive replication. Once cytosolic, Francisella becomes a target of an autophagy-mediated process. The mechanisms by which autophagy plays a role in replication of this cytosolic pathogen have not been fully elucidated. In vitro, F. tularensis avoids degradation via autophagy and the autophagy process provides nutrients that support its intracellular replication, but the role of autophagy in vivo is unknown. Here, we investigated the role of autophagy in the pathogenesis of tularemia by using transgenic mice deficient in Atg5 in the myeloid lineage. The infection of Atg5-deficient mice with Francisella tularensis subsp. holarctica live vaccine strain (LVS) resulted in increased survival, significantly reduced bacterial burden in the mouse organs, and less severe histopathological changes in the spleen, liver and lung tissues. The data highlight the contribution of Atg5 in the pathogenesis of tularemia in vivo.
- Subjects
FRANCISELLA tularensis; TRANSGENIC mice; ANIMAL species; MICE; PATHOLOGY; INTRACELLULAR pathogens
- Publication
Microorganisms, 2020, Vol 8, Issue 10, p1531
- ISSN
2076-2607
- Publication type
Article
- DOI
10.3390/microorganisms8101531