Browsing by keyword "Rickettsiaceae Infections"
Now showing items 1-2 of 2
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Innate immune responses to endosymbiotic Wolbachia bacteria in Brugia malayi and Onchocerca volvulus are dependent on TLR2, TLR6, MyD88, and Mal, but not TLR4, TRIF, or TRAMThe discovery that endosymbiotic Wolbachia bacteria play an important role in the pathophysiology of diseases caused by filarial nematodes, including lymphatic filariasis and onchocerciasis (river blindness) has transformed our approach to these disabling diseases. Because these parasites infect hundreds of millions of individuals worldwide, understanding host factors involved in the pathogenesis of filarial-induced diseases is paramount. However, the role of early innate responses to filarial and Wolbachia ligands in the development of filarial diseases has not been fully elucidated. To determine the role of TLRs, we used cell lines transfected with human TLRs and macrophages from TLR and adaptor molecule-deficient mice and evaluated macrophage recruitment in vivo. Extracts of Brugia malayi and Onchocerca volvulus, which contain Wolbachia, directly stimulated human embryonic kidney cells expressing TLR2, but not TLR3 or TLR4. Wolbachia containing filarial extracts stimulated cytokine production in macrophages from C57BL/6 and TLR4(-/-) mice, but not from TLR2(-/-) or TLR6(-/-) mice. Similarly, macrophages from mice deficient in adaptor molecules Toll/IL-1R domain-containing adaptor-inducing IFN-beta and Toll/IL-1R domain-containing adaptor-inducing IFN-beta-related adaptor molecule produced equivalent cytokines as wild-type cells, whereas responses were absent in macrophages from MyD88(-/-) and Toll/IL-1R domain-containing adaptor protein (TIRAP)/MyD88 adaptor-like (Mal) deficient mice. Isolated Wolbachia bacteria demonstrated similar TLR and adaptor molecule requirements. In vivo, macrophage migration to the cornea in response to filarial extracts containing Wolbachia was dependent on TLR2 but not TLR4. These results establish that the innate inflammatory pathways activated by endosymbiotic Wolbachia in B. malayi and O. volvulus filaria are dependent on TLR2-TLR6 interactions and are mediated by adaptor molecules MyD88 and TIRAP/Mal.
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Rochalimaea elizabethae sp. nov. isolated from a patient with endocarditisA Rochalimaea-like organism (strain F9251) was isolated from a patient with endocarditis after blood drawn for culture before antimicrobial therapy was subcultured onto blood and chocolate agars and incubated for 2 weeks in 5% CO2. The strain was phenotypically similar to known Rochalimaea species. The cellular fatty acid composition of strain F9251 was close to but distinct from those of the three known Rochalimaea species and was most similar to that of R. vinsonii. Labeled DNA from strain F9251 was 59 to 67% related to DNAs from type strains of the three described Rochalimaea species, and its 16S rRNA gene sequence was 98.9% or more homologous to their 16S rRNA gene sequences. These findings support classification of F9251 as a new Rochalimaea species, for which the name Rochalimaea elizabethae sp. nov. is proposed. The patient infected with the organism had large bacterial vegetations on his aortic valve and was cured with antibiotics and valve-replacement surgery. Recognition of the procedures required to identify this and other Rochalimaea species suggests that clinical laboratories should prolong the incubation times of cultures of blood and tissue from patients with suspected endocarditis, patients with fever of unknown origin, and immunocompromised patients with fever so that the full spectrum of disease caused by these organisms can be recognized.
