Rickettsia-Macrophage Interactions: Host Cell Responses toRickettsia akariandRickettsia typhi

Radulović, Suzana; Price, P. W.; Beier, Magda S.; Gaywee, Jariyanart; Macaluso, Jacqueline A.; Azad, Abdu F.

doi:10.1128/iai.70.5.2576-2582.2002

Cited by 56 publications

(49 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, intact R. typhi particles were detectable in the areas of macrophage infiltration by histological staining, indicating bacterial replication and incapability of these cells to kill R. typhi. In line with these findings, R. typhi has been shown to survive and to replicate in murine and human macrophages (73,74), which is also true for other rickettsiae, such as O. tsutsugamushi (18,19) and Rickettsia akari (75). Therefore, it is not clear whether these cells are recruited to the CNS for defense against R. typhi by phagocytosis and killing of intracellular particles or whether they may serve as a kind of shuttle.…”

Section: Discussionsupporting

confidence: 60%

Persisting Rickettsia typhi Causes Fatal Central Nervous System Inflammation

et al. 2016

View full text Add to dashboard Cite

bRickettsioses 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.

show abstract

Section: Discussionsupporting

confidence: 60%

Persisting Rickettsia typhi Causes Fatal Central Nervous System Inflammation

et al. 2016

View full text Add to dashboard Cite

show abstract

“…We propose that infection of nonendothelial cells has been overlooked during prior examinations of SFG Rickettsia pathogenesis and that our newly developed techniques have allowed a more complete analysis of infection. This idea is supported by several in vitro and ex vivo studies that have demonstrated that rickettsial species can infect and grow within macrophages and hepatocytes (30)(31)(32)(33), suggesting that the interaction with cells other than those of the endothelium may be an important and underappreciated aspect of the pathogenesis of rickettsial diseases. Additionally, IHC and immunofluorescence microscopy both display intact bacilli, and nonendothelial cells frequently contain multiple plasmid-transformed R. conorii bacteria ( Fig.…”

Section: Discussionmentioning

confidence: 53%

Nonselective Persistence of a Rickettsia conorii Extrachromosomal Plasmid during Mammalian Infection

et al. 2016

View full text Add to dashboard Cite

Scientific analysis of the genus Rickettsia is undergoing a rapid period of change with the emergence of viable genetic tools. The development of these tools for the mutagenesis of pathogenic bacteria will permit forward genetic analysis of Rickettsia pathogenesis. Despite these advances, uncertainty still remains regarding the use of plasmids to study these bacteria in in vivo mammalian models of infection, namely, the potential for virulence changes associated with the presence of extrachromosomal DNA and nonselective persistence of plasmids in mammalian models of infection. Here, we describe the transformation of Rickettsia conorii Malish 7 with the plasmid pRam18dRGA[AmTrCh]. Transformed R. conorii stably maintains this plasmid in infected cell cultures, expresses the encoded fluorescent proteins, and exhibits growth kinetics in cell culture similar to those of nontransformed R. conorii. Using a well-established murine model of fatal Mediterranean spotted fever, we demonstrate that R. conorii(pRam18dRGA[AmTrCh]) elicits the same fatal outcomes in animals as its untransformed counterpart and, importantly, maintains the plasmid throughout infection in the absence of selective antibiotic pressure. Interestingly, plasmid-transformed R. conorii was readily observed both in endothelial cells and within circulating leukocytes. Together, our data demonstrate that the presence of an extrachromosomal DNA element in a pathogenic rickettsial species does not affect either in vitro proliferation or in vivo infectivity in models of disease and that plasmids such as pRam18dRGA[AmTrCh] are valuable tools for the further genetic manipulation of pathogenic rickettsiae.

show abstract

“…Mycobacterium species, Legionella pneumophila, Listeria monocytogenes and mammalian rickettsiae are pathogens which have evolved strategies to avoid eradication by macrophage bactericidal mechanisms [24][25][26][27][28]. Among other survival strategies, mycobacteria prevent acidification of the phagosome and phagosome-lysosome fusion, thereby precluding digestion by lysosomal contents [26,[29][30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%