Nejvíce citovaný článek - PubMed ID 31097026
Metamorphoses of Lyme disease spirochetes: phenomenon of Borrelia persisters
Borrelia burgdorferi sensu lato is a species complex of pleomorphic spirochetes, including species that cause Lyme disease (LD) in humans. In addition to classic spiral forms, these bacteria are capable of creating morphological forms referred to as round bodies and aggregates. The subject of discussion is their possible contribution to the persistence of infection or post-infection symptoms in LD. This study investigates the immunological properties of these forms by monitoring reactivity with early (n = 30) and late stage (n = 30) LD patient sera and evaluating the immune response induced by vaccination of mice. In patient sera, we found a quantitative difference in reactivity with individual morphotypes, when aggregates were recognized most intensively, but the difference was statistically significant in only half of the tested strains. In post-vaccination mouse sera, we observed a statistically significant higher reactivity with antigens p83 and p25 (OspC) in mice vaccinated with aggregates compared to mice vaccinated with spiral forms. The importance of the particulate nature of the antigen for the induction of a Th1-directed response has also been demonstrated. In any of morphological forms, the possibility of inducing antibodies cross-reacting with human nuclear and myositis specific/associated autoantigens was not confirmed by vaccination of mice.
- MeSH
- antigeny bakteriální MeSH
- Borrelia burgdorferi komplex * MeSH
- Borrelia burgdorferi * MeSH
- lidé MeSH
- lymeská nemoc * mikrobiologie MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigeny bakteriální MeSH
Infection with Borrelia burgdorferi often triggers pathophysiologic perturbations that are further augmented by the inflammatory responses of the host, resulting in the severe clinical conditions of Lyme disease. While our apprehension of the spatial and temporal integration of the virulence determinants during the enzootic cycle of B. burgdorferi is constantly being improved, there is still much to be discovered. Many of the novel virulence strategies discussed in this review are undetermined. Lyme disease spirochaetes must surmount numerous molecular and mechanical obstacles in order to establish a disseminated infection in a vertebrate host. These barriers include borrelial relocation from the midgut of the feeding tick to its body cavity and further to the salivary glands, deposition to the skin, haematogenous dissemination, extravasation from blood circulation system, evasion of the host immune responses, localization to protective niches, and establishment of local as well as distal infection in multiple tissues and organs. Here, the various well-defined but also possible novel strategies and virulence mechanisms used by B. burgdorferi to evade obstacles laid out by the tick vector and usually the mammalian host during colonization and infection are reviewed.
- Klíčová slova
- Borrelia burgdorferi, Lyme disease, clinical manifestations, pathogenicity, tick-borne disease, virulence determinants,
- MeSH
- Borrelia burgdorferi * genetika MeSH
- faktory virulence MeSH
- lidé MeSH
- lymeská nemoc * MeSH
- savci MeSH
- virulence MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- faktory virulence MeSH
Lyme disease (LD) spirochetes are well known to be able to disseminate into the tissues of infected hosts, including humans. The diverse strategies used by spirochetes to avoid the host immune system and persist in the host include active immune suppression, induction of immune tolerance, phase and antigenic variation, intracellular seclusion, changing of morphological and physiological state in varying environments, formation of biofilms and persistent forms, and, importantly, incursion into immune-privileged sites such as the brain. Invasion of immune-privileged sites allows the spirochetes to not only escape from the host immune system but can also reduce the efficacy of antibiotic therapy. Here we present a case of the detection of spirochetal DNA in multiple loci in a LD patient's post-mortem brain. The presence of co-infection with Borrelia burgdorferi sensu stricto and Borrelia garinii in this LD patient's brain was confirmed by PCR. Even though both spirochete species were simultaneously present in human brain tissue, the brain regions where the two species were detected were different and non-overlapping. The presence of atypical spirochete morphology was noted by immunohistochemistry of the brain samples. Atypical morphology was also found in the tissues of experimentally infected mice, which were used as a control.
- Klíčová slova
- Borrelia burgdorferi, Borrelia garinii, Lyme disease, co-infection, human brain, immunohistochemistry, molecular detection, neuroborreliosis, persistence,
- MeSH
- Borrelia burgdorferi komplex * genetika MeSH
- Borrelia burgdorferi * genetika MeSH
- Borrelia * genetika MeSH
- lidé MeSH
- lymeská nemoc * MeSH
- mozek MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Most patients suffering from Lyme disease are effectively treated with antibiotics. In some patients, however, problems persist for a long time despite appropriate therapy. The term post-treatment Lyme disease syndrome (PTLDS) is currently used for this condition in scientific literature. The pathogenesis is still not precisely known, but the involvement of immunopathological mechanisms is assumed. In our study, we analyzed the presence of autoantibodies including myositis-specific (MSA) and myositis-associated autoantibodies (MAA) in patients with laboratory proven history of Lyme disease and with clinical symptoms of PTLDS. A total of 59 patients meeting the criteria for PTLDS were enrolled in this study. The control group consisted of 40 patients undergoing differential diagnosis of neurological disorders without clinical and/or laboratory-proven history of Lyme disease. The presence of autoantibodies was determined by immunoblot methods and positive samples were further tested for serum creatine kinase (CK) and myoglobin levels. The presence of myositis autoantibodies was detected in 18 subjects with suspected PTLDS (30.5%), but only in 5% of control subjects exhibiting no evidence of Lyme disease history. The difference was statistically significant (p = 0.002). The subsequent biochemical analysis of muscle-damage markers in positive subjects found a mild elevation in six MSA/MAA-positive PTLDS patients. The study detected raised MSA/MAA autoantibodies formation in the group of PTLDS patients raising the question about their involvement in the pathogenesis of this syndrome.
- Klíčová slova
- Lyme disease, autoantibodies, myositis, post-treatment Lyme disease syndrome,
- Publikační typ
- časopisecké články MeSH
The hypothesized importance of coinfections in the pathogenesis of post-treatment Lyme disease syndrome (PTLDS) leads to the use of combined, ongoing antimicrobial treatment in many cases despite the absence of symptoms typical of the presence of infection with specific pathogens. Serum samples from 103 patients with suspected post-treatment Lyme disease syndrome were tested for the presence of antibodies to the major tick-borne pathogens Anaplasma phagocytophilum, Bartonella henselae/Bartonella quinatana, and Babesia microti. Although the presence of anti-Anaplasma antibodies was detected in 12.6% of the samples and anti-Bartonella antibodies in 9.7% of the samples, the presence of antibodies against both pathogens in the same samples or anti-Babesia antibodies in the selected group of patients could not be confirmed. However, we were able to detect autoantibodies, mostly antinuclear, in 11.6% of the patients studied. Our results are in good agreement with previously published studies showing the presence of a wide spectrum of autoantibodies in some patients with complicated forms of Lyme disease and post-treatment Lyme disease syndrome, but they do not reveal a significant influence of co-infections on the development of PTLDS in the studied group of patients.
- Klíčová slova
- Anaplasma, Babesia, Bartonella, Lyme disease, co-infection, post-treatment Lyme disease syndrome, seroprevalence, ticks,
- Publikační typ
- časopisecké články MeSH
Lyme borreliosis is a bacterial infection that can be spread to humans by infected ticks and may severely affect many organs and tissues. Nearly four decades have elapsed since the discovery of the disease agent called Borrelia burgdorferi. Although there is a plethora of knowledge on the infectious agent and thousands of scientific publications, an effective way on how to combat and prevent Lyme borreliosis has not been found yet. There is no vaccine for humans available, and only one active vaccine program in clinical development is currently running. A spirited search for possible disease interventions is of high public interest as surveillance data indicates that the number of cases of Lyme borreliosis is steadily increasing in Europe and North America. This review provides a condensed digest of the history of vaccine development up to new promising vaccine candidates and strategies that are targeted against Lyme borreliosis, including elements of the tick vector, the reservoir hosts, and the Borrelia pathogen itself.
- Klíčová slova
- Anti-tick strategies, Human pathogen, Lyme borreliosis, Public health, Vaccine candidates,
- MeSH
- bakteriální vakcíny genetika imunologie MeSH
- Borrelia burgdorferi genetika imunologie fyziologie MeSH
- infekce přenášené vektorem MeSH
- klíšťata mikrobiologie MeSH
- lidé MeSH
- lymeská nemoc imunologie mikrobiologie prevence a kontrola MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- bakteriální vakcíny MeSH