Lyme disease, the most common vector-borne illness in North America, is caused by the spirochete Borrelia burgdorferi. Infection begins in the skin following a tick bite and can spread to the hearts, joints, nervous system, and other organs. Diverse host responses influence the level of B. burgdorferi infection in mice and humans. Using a systems biology approach, we examined potential molecular interactions between human extracellular and secreted proteins and B. burgdorferi. A yeast display library expressing 1031 human extracellular proteins was probed against 36 isolates of B. burgdorferi sensu lato. We found that human Peptidoglycan Recognition Protein 1 (PGLYRP1) interacted with the vast majority of B. burgdorferi isolates. In subsequent experiments, we demonstrated that recombinant PGLYRP1 interacts with purified B. burgdorferi peptidoglycan and exhibits borreliacidal activity, suggesting that vertebrate hosts may use PGLYRP1 to identify B. burgdorferi. We examined B. burgdorferi infection in mice lacking PGLYRP1 and observed an increased spirochete burden in the heart and joints, along with splenomegaly. Mice lacking PGLYRP1 also showed signs of immune dysregulation, including lower serum IgG levels and higher levels of IFNγ, CXCL9, and CXCL10.Taken together, our findings suggest that PGLYRP1 plays a role in the host's response to B. burgdorferi and further demonstrate the utility of expansive yeast display screening in capturing biologically relevant interactions between spirochetes and their hosts.
- MeSH
- Borrelia burgdorferi fyziologie MeSH
- cytokiny genetika metabolismus MeSH
- genová knihovna MeSH
- lidé MeSH
- lymeská nemoc mikrobiologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural 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.
- 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
A wide range of viral agents is associated with the development of acute myocarditis and its possible chronic sequela, dilated cardiomyopathy (DCM). There is also increasing evidence that Borrelia burgdorferi (Bb) is associated with DCM in endemic regions for Bb infection. This study sought to use electron microscopy to prospectively analyze the presence of viruses and Bb within the myocardium of 40 subjects with preserved left ventricular (LV) ejection fraction and 40 patients with new-onset unexplained DCM during the same time period. Virus particles were found within the myocardium of 23 subjects (58%) of both cohorts studied, yet there was no statistically significant difference in virus family presence between those with DCM versus those with preserved LV systolic function. In contrast, Bb was detected only in those subjects with DCM (0 versus 5 subjects; p ˂ 0.05). Polymerase chain reaction was performed on samples from patients who were positive for Bb according to electron microscopy, and Bb was confirmed in 4 out of 5 individuals. Our results demonstrate that the prevalence of viral particles does not differ between subjects with preserved LV systolic function versus those with DCM and therefore suggests that the mere presence of a viral agent within the myocardium is not sufficient to establish a clear link with the development of DCM. In contrast, the presence of Bb was found only within myocardial samples of patients with DCM; this finding supports the idea of a causal relationship between Bb infection and DCM development.
- MeSH
- antivirové látky škodlivé účinky terapeutické užití MeSH
- Borrelia burgdorferi genetika izolace a purifikace fyziologie ultrastruktura MeSH
- dilatační kardiomyopatie mikrobiologie patofyziologie virologie MeSH
- elektronová mikroskopie MeSH
- funkce levé komory srdeční MeSH
- krevní tlak MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymeská nemoc klasifikace mikrobiologie patofyziologie MeSH
- myokard ultrastruktura MeSH
- prospektivní studie MeSH
- senioři MeSH
- srdce mikrobiologie patofyziologie virologie MeSH
- virové nemoci komplikace farmakoterapie virologie MeSH
- viry klasifikace genetika izolace a purifikace ultrastruktura MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Reaction of vertebrate serum complement with different Borrelia burgdorferi sensu lato species is used as a basis in determining reservoir hosts among domesticated and wild animals. Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii were tested for their sensitivity to sera of exotic vertebrate species housed in five zoos located in the Czech Republic. We confirmed that different Borrelia species have different sensitivity to host serum. We found that tolerance to Borrelia infection possessed by hosts might differ among individuals of the same genera or species and is not affected by host age or sex. Of all zoo animals included in our study, carnivores demonstrated the highest apparent reservoir competency for Lyme borreliosis spirochetes. We showed that selected exotic ungulate species are tolerant to Borrelia infection. For the first time we showed the high tolerance of Siamese crocodile to Borrelia as compared to the other studied reptile species. While exotic vertebrates present a limited risk to the European human population as reservoirs for the causative agents of Lyme borreliosis, cases of incidental spillover infection could lead to successful replication of the pathogens in a new host, changing the status of selected exotic species and their role in pathogen emergence or maintenance. The question if being tolerant to pathogen means to be a competent reservoir host still needs an answer, simply because the majority of exotic animals might never be exposed to spirochetes in their natural environment.
- MeSH
- Borrelia burgdorferi fyziologie MeSH
- komplement farmakologie MeSH
- lymeská nemoc imunologie mikrobiologie veterinární MeSH
- obratlovci imunologie MeSH
- zdroje nemoci MeSH
- zvířata v ZOO MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Type I interferon (IFN), mainly produced by dendritic cells (DCs), is critical in the host defence against tick-transmitted pathogens. Here, we report that salivary cysteine protease inhibitor from the hard tick Ixodes scapularis, sialostatin L2, affects IFN-β mediated immune reactions in mouse dendritic cells. Following IFN receptor ligation, the Janus activated kinases/signal transducer and activator of transcription (JAK/STAT) pathway is activated. We show that sialostatin L2 attenuates phosphorylation of STATs in spleen dendritic cells upon addition of recombinant IFN-β. LPS-stimulated dendritic cells release IFN-β which in turn leads to the induction of IFN-stimulated genes (ISG) through JAK/STAT pathway activation. The induction of two ISG, interferon regulatory factor 7 (IRF-7) and IP-10, was suppressed by sialostatin L2 in LPS-stimulated dendritic cells. Finally, the interference of sialostatin L2 with IFN action led to the enhanced replication of tick-borne encephalitis virus in DC. In summary, we present here that tick salivary cystatin negatively affects IFN-β responses which may consequently increase the pathogen load after transmission via tick saliva.
- MeSH
- Borrelia burgdorferi fyziologie MeSH
- cystatiny imunologie MeSH
- dendritické buňky imunologie MeSH
- fosforylace MeSH
- interferon beta imunologie MeSH
- interferonový regulační faktor 7 imunologie MeSH
- klíště imunologie mikrobiologie MeSH
- lipopolysacharidy imunologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- receptory cytokinové imunologie MeSH
- receptory interferonů metabolismus MeSH
- slinné cystatiny imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Analysis of Borrelia burgdorferi ospC types from the southeastern U.S.A. supported the common belief that various ospC types are geographically restricted and host specific. Being widely distributed in the region, the southeastern population of B. burgdorferi is represented by a surprisingly small number of ospC types. Types B, G and H are dominant or common and are invasive, while scarce type L, restricted mostly to the southeastern U.S.A., is believed to rarely if ever cause human Lyme disease. OspC type B and L strains are represented in the region at the same rate, however their distribution among tick vectors and vertebrate hosts is unequal. FINDINGS: Direct diagnostics was used to analyze the ability of B. burgdorferi ospC type L strains to disseminate into host tissues. Mice were infected by subcutaneous injections of B. burgdorferi strains of various ospC types with different invasive capability. Spirochete levels were examined in ear, heart, bladder and joint tissues. Noninfected I. ricinus larvae were fed on infected mice until repletion. Infection rates were determined in molted nymphs. Infected nymphs were then fed on naïve mice, and spirochete transmission from infected nymphs to mice was confirmed. CONCLUSIONS: B. burgdorferi ospC type L strains from the southeastern U.S.A. have comparable potential to disseminate into host tissues as ospC types strains commonly associated with human Lyme disease in endemic European and North American regions. We found no difference in the invasive ability of ospC type B and L strains originated either from tick vectors or vertebrate hosts.
- MeSH
- antigeny bakteriální genetika metabolismus MeSH
- Borrelia burgdorferi klasifikace fyziologie MeSH
- lidé MeSH
- lymeská nemoc epidemiologie mikrobiologie MeSH
- myši MeSH
- proteiny vnější bakteriální membrány genetika metabolismus MeSH
- regulace genové exprese u bakterií fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
- jihovýchod USA MeSH
In vitro effect of salivary gland extract from fed Ixodes ricinus, the competent vector of Lyme borreliosis in Europe, on the growth of Borrelia burgdorferi sensu lato (B. garinii, B. afzelii and B. burgdorferi sensu stricto) was examined in BSK-H medium. Motility rate, concentration of motile spirochetes and their morphology were estimated at intervals of 0, 2, 4, 6 and 8 days using darkfield microscopy. Salivary gland extract derived from I. ricinus stimulated markedly the growth of three genomic species of borreliae. The results confirm a substantial role of salivary glands in the mechanism of pathogen transmission to vertebrate host.
- MeSH
- Borrelia burgdorferi cytologie účinky léků růst a vývoj fyziologie MeSH
- buněčné extrakty chemie farmakologie MeSH
- klíště MeSH
- kultivační média chemie MeSH
- lokomoce MeSH
- mikrobiální viabilita MeSH
- mikroskopie MeSH
- růstové látky farmakologie MeSH
- slinné žlázy chemie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Lymská borelióza (LB) je v súčasnosti najrozšírenejšou antropozoonózou prenášanou kliešťami v Európe, Ázii a Severnej Amerike. Pre zvládnutie nástrah, ktoré borélie, vybavené mimoriadnou odolnosťou v prostredí a v organizme, predstavujú aj pre človeka, autori upozornili prehľadne aj na novšie znalosti o štruktúre borélií a ich chovaní sa v hostiteľovi, o vektoroch a rezervoároch, o geograficky špecifikovaných genotypoch borélií s ich rozdielnym orgánovým tropizmom. Poznatky by mali slúžiť k ochrane zdravia, zlepšeniu odhaľovania aj tých borelióz, ktoré sa skrývajú hlavne pri chronickom priebehu pod inými diagnózami a vyžadujú si adekvátnu liečbu a pracovné zaradenie. Autori vychádzali v práci zo stúpajúceho trendu výskytu LB na Slovensku v rokoch 1998–2007, kde je najvyšší výskyt vo vekovej skupine 55–64-ročnej populácie. Profesionálna LB sa v SR nevykazuje v zdravotníckej štatistike UZIŠ samostatne (počty sú súčasťou sledovanej položky infekčných profesionálnych ochorení spolu). Autori preto zberali údaje o výskyte profesionálnej LB z jednotlivých kliník a oddelení pracovného lekárstva SR. Potvrdili, že výskyt profesionálnej LB medzi rokmi 2001–2007 má tiež vzostupnú tendenciu. V rokoch 2001–2007 bolo na Slovensku hlásených spolu 102 prípadov profesionálnej LB, s najvyššími počtami v Západoslovenskom kraji, v oblasti Považia a Žarnovice. LB tvorí 4–6 % zo všetkých ročne hlásených chorôb z povolania v SR. V užšom 55-člennom súbore pacientov s profesionálnou LB zo stredoslovenského regionu autori retrospektívne zistili prevahu robotníckych prác v ťažbe dreva a v pestevnej činnosti u zamestnancov lesného hospodárstva. Prierezovo zaznamenali klinický nález v období hlásenia choroby z povolania (dominovali chronicky prebiehajúce LB s neurologickou a kĺbnosvalovou symptomatikou). Priemerný vek pri hlásení profesionálnej LB bol 48,55 ± 9,53 rokov (x ± SD), kulminovala skupina 45–54-ročných, v ktorej bol vyšší podiel žien. Ochorenie si u polovice postihnutých vyžiadalo zmenu pracovného zaradenia, niekedy s invaliditou, odchodom do starobného dôchodku. Postihnutie LB v produktívnom veku vyjadruje aj mieru spoločenskej závažnosti LB, kde sú o. i. následne problémy získať vhodné pracovné uplatnenie, zodpovedajúce miere trvalej straty zdravotnej spôsobilosti. Autori v prehľade uvádzajú kritéria, o ktoré sa opierajú pri diagnostike profesionálnej LB. V závere rozoberajú súčasné, pomerne obmedzené možnosti prevencie LB.
Lyme borreliosis (LB) is currently the most frequent anthropozoonosis transferred by ticks in Europe, Asia and North America. In their review, authors highlighted the special resistance of Borrelias in the environment and organism, current knowledge on the structure of Borrelias and their interaction with the host organism, vectors and reservoirs, geographically specific genotypes with different organ tropism. The knowledge should contribute to the protection of health, improvement of detection of Borrelias which are hidden under other diagnoses in chronic conditions and require adequate treatment and working position. The authors refer to the increasing trend in occurrence of LB in Slovakia in 1998–2007, with the highest occurrence in the age group of 55–64 years. Professional LB is not reported separately in the health statics in SR (numbers are included into the item of infectious professional diseases altogether). Therefore, they collected data on the occurrence of professional LB from individual clinics and departments of occupational medicine in SR. They proved that the occurrence of professional LB between 2001 and 2007 had an increasing trend. Between 2001 and 2007, 102 cases of professional LB were reported in Slovakia, with the highest rates in the West Slovakia Region (Považie, Žarnovica). LB forms 4–6% of all occupational diseases reported annually in SR. The authors found retrospectively predominance of workers in the wood production and employees in the forestry in the narrow 55 member sample of patients with professional LB from the Central Slovakia Region. They registered the clinical findings at the time of reporting the occupational disease (predominantly chronic LB with neurological and arthromuscular symptomatology). The mean age at reporting professional LB was 48.55 ± 9.53 years (x ± SD), the group of 45–54 years old culminated, with the higher proportion of women. The disease required the change in working position in a half of patients, sometimes also disability or retirement. LB in the productive age reflects the social significance with subsequent problems related to suitable employment adequate to long-term health disability. The authors presented the criteria used in the diagnostics of professional LB. Finally, they mentioned current quite limited options in prevention of LB.
- MeSH
- Borrelia burgdorferi fyziologie patogenita MeSH
- diagnostické techniky a postupy MeSH
- diferenciální diagnóza MeSH
- financování organizované MeSH
- infekce bakteriemi rodu Borrelia prevence a kontrola přenos MeSH
- klinické laboratorní techniky MeSH
- lidé MeSH
- longitudinální studie MeSH
- lymeská nemoc epidemiologie farmakoterapie přenos MeSH
- nemoci z povolání diagnóza MeSH
- pracovní lékařství MeSH
- přenos infekční nemoci prevence a kontrola MeSH
- primární prevence MeSH
- příznaky a symptomy MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- grafy a diagramy MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
- MeSH
- Borrelia burgdorferi fyziologie izolace a purifikace MeSH
- finanční podpora výzkumu jako téma MeSH
- klinické laboratorní techniky metody MeSH
- lidé MeSH
- lymeská nemoc diagnóza imunologie mikrobiologie MeSH
- protilátky bakteriální analýza MeSH
- recidiva imunologie mikrobiologie MeSH
- tělesné tekutiny mikrobiologie MeSH
- tkáně mikrobiologie MeSH
- Check Tag
- lidé MeSH
