Persisting Rickettsia typhi Causes Fatal Central Nervous System Inflammation
| Autor: | Stefanie Papp, Svenja Kuehl, Kristin Moderzynski, Ulricke Richardt, Anke Osterloh, Bernhard Fleischer |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Programmed cell death Immunology Nitric Oxide Synthase Type II Inflammation Spleen Biology Microbiology 03 medical and health sciences Central Nervous System Infections 0302 clinical medicine Immunity Rickettsia typhi medicine Animals Lung Homeodomain Proteins Mice Knockout Mice Inbred BALB C Microglia Brain Typhus Endemic Flea-Borne Bacterial Infections Acquired immune system medicine.disease biology.organism_classification Mice Inbred C57BL 030104 developmental biology Infectious Diseases medicine.anatomical_structure Chronic Disease bacteria Parasitology medicine.symptom 030217 neurology & neurosurgery Typhus |
| Zdroj: | Infection and Immunity. 84:1615-1632 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00034-16 |
| Popis: | Rickettsioses are emerging febrile diseases caused by obligate intracellular bacteria belonging to the family Rickettsiaceae. Rickettsia typhi belongs to the typhus group (TG) of this family and is the causative agent of endemic typhus, a disease that can be fatal. In the present study, we analyzed the course of R. typhi infection in C57BL/6 RAG1 −/− mice. Although these mice lack adaptive immunity, they developed only mild and temporary symptoms of disease and survived R. typhi infection for a long period of time. To our surprise, 3 to 4 months after infection, C57BL/6 RAG1 −/− mice suddenly developed lethal neurological disorders. Analysis of these mice at the time of death revealed high bacterial loads, predominantly in the brain. This was accompanied by a massive expansion of microglia and by neuronal cell death. Furthermore, high numbers of infiltrating CD11b + macrophages were detectable in the brain. In contrast to the microglia, these cells harbored R. typhi and showed an inflammatory phenotype, as indicated by inducible nitric oxide synthase (iNOS) expression, which was not observed in the periphery. Having shown that R. typhi persists in immunocompromised mice, we finally asked whether the bacteria are also able to persist in resistant C57BL/6 and BALB/c wild-type mice. Indeed, R. typhi could be recultivated from lung, spleen, and brain tissues from both strains even up to 1 year after infection. This is the first report demonstrating persistence and reappearance of R. typhi , mainly restricted to the central nervous system in immunocompromised mice. |
| Databáze: | OpenAIRE |
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