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BioRxiv : the Preprint Server For... May 2024ticks are an important vector for at least six tick-borne human pathogens, including the predominant North American Lyme disease spirochete . The ability for these...
UNLABELLED
ticks are an important vector for at least six tick-borne human pathogens, including the predominant North American Lyme disease spirochete . The ability for these ticks to survive in nature is credited, in part, to their ability to feed on a variety of hosts without excessive activation of the proinflammatory branch of the vertebrate immune system. While the ability for nymphal ticks to feed on a variety of hosts has been well-documented, the host-parasite interactions between larval and different vertebrate hosts is relatively unexplored. Here we report on the changes in the vertebrate transcriptome present at the larval tick bite site using the natural host deermouse, a non-natural rodent host (BALB/c), and humans. We note substantially less evidence of activation of canonical proinflammatory pathways in compared to BALB/c mice and pronounced evidence of inflammation in humans. Pathway enrichment analyses revealed a particularly strong signature of interferon gamma, tumor necrosis factor, and interleukin 1 signaling at the BALB/c and human tick bite site. We also note that bite sites on BALB/c mice and humans, but not deermice, show activation of wound-healing pathways. These data provide molecular evidence of the coevolution between larval and as well as expand our overall understanding of feeding.
SIGNIFICANCE
tick bites expose humans to numerous diseases in North America. While larval tick feeding enables pathogens to enter the tick population and eventually spread to humans, how larval ticks interact with mammals has been understudied compared to other tick stages. Here we examined the transcriptomic response of a natural rodent host ( ), a non-native rodent host ( ), and an incidental host (humans). We find that there are differences in how all three species respond to larval , with the natural host producing the smallest transcriptomic signature of a canonical proinflammatory immune response and the incidental human host producing the most robust signature of inflammation in response to the larval tick. These data expand our understanding of the pressures on ticks in the wild and inform our ability to model these interactions in laboratory settings.
PubMed: 38746284
DOI: 10.1101/2024.05.02.592193 -
BioRxiv : the Preprint Server For... Apr 2024Innate immunity, the first line of defense against pathogens, relies on efficient elimination of invading agents by phagocytes. In the co-evolution of host and pathogen,...
Innate immunity, the first line of defense against pathogens, relies on efficient elimination of invading agents by phagocytes. In the co-evolution of host and pathogen, pathogens developed mechanisms to dampen and evade phagocytic clearance. Here, we report that bacterial pathogens can evade clearance by macrophages through mimicry at the mammalian anti-phagocytic "don't eat me" signaling axis between CD47 (ligand) and SIRPα (receptor). We identified a protein, P66, on the surface of that, like CD47, is necessary and sufficient to bind the macrophage receptor SIRPα. Expression of the gene encoding the protein is required for bacteria to bind SIRPα or a high-affinity CD47 reagent. Genetic deletion of increases phagocytosis by macrophages. Blockade of P66 during infection promotes clearance of the bacteria. This study demonstrates that mimicry of the mammalian anti-phagocytic protein CD47 by inhibits macrophage-mediated bacterial clearance. Such a mechanism has broad implications for understanding of host-pathogen interactions and expands the function of the established innate immune checkpoint receptor SIRPα. Moreover, this report reveals P66 as a novel therapeutic target in the treatment of Lyme Disease.
PubMed: 38746193
DOI: 10.1101/2024.04.29.591704 -
Scientific Reports May 2024Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system that affects mainly young people. It is believed that the autoimmune process...
Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system that affects mainly young people. It is believed that the autoimmune process observed in the pathogenesis of MS is influenced by a complex interaction between genetic and environmental factors, including infectious agents. The results of this study suggest the protective role of Toxoplasma gondii infections in MS. Interestingly, high Toxoplasma IgM seropositivity in MS patients receiving immunomodulatory drugs (IMDs) was identified. On the other hand, Borrelia infections seem to be positively associated with MS. Although the interpretation of our results is limited by the retrospective nature of the studies, the results strongly indicate that further experimental and clinical studies are needed to explain the role of infectious agents in the development and pathophysiological mechanisms of MS.
Topics: Humans; Multiple Sclerosis; Toxoplasmosis; Poland; Seroepidemiologic Studies; Female; Toxoplasma; Male; Adult; Lyme Disease; Borrelia burgdorferi; Middle Aged; Immunoglobulin M; Retrospective Studies; Young Adult
PubMed: 38744898
DOI: 10.1038/s41598-024-61714-y -
Cureus Apr 2024Infection with spirochetes can cause Lyme neuroborreliosis (LNB). Neuroborreliosis presenting as encephalitis is a rare manifestation. We present a 72-year-old...
Infection with spirochetes can cause Lyme neuroborreliosis (LNB). Neuroborreliosis presenting as encephalitis is a rare manifestation. We present a 72-year-old male patient hospitalized after three days of confusion and altered mental status. Initial computerized tomography (CT) and magnetic resonance imaging (MRI) of the brain were both unremarkable. Lumbar puncture showed an elevated number of white blood cells, elevated protein, and normal glucose levels in the cerebrospinal fluid (CSF), normal electroencephalogram (EEG), and negative tests for common microorganisms in the CSF. The patient received treatment with acyclovir and ceftriaxone. Lumbar puncture repeated on day 16 showed a decreasing number of white blood cells. A repeated MRI showed white matter edema, interpreted as encephalitis, while a repeated EEG showed signs of a non-specific cerebral lesion. The first lumbar puncture revealed intrathecal immunoglobulin M (IgM) antibodies against and was positive for DNA using real-time PCR, and the following lumbar puncture showed both IgM and IgG intrathecal antibody production. These results thus confirmed the diagnosis of Lyme encephalitis. The patient improved clinically and was discharged after treatment with ceftriaxone for three weeks. Encephalitis due to LNB should be considered as a differential diagnosis in cases with unexplained neurological symptoms. Changes in MRI and/or EEG might occur late in the course of the disease, underlining the need for repeated tests in unresolved cases.
PubMed: 38725777
DOI: 10.7759/cureus.57882 -
PloS One 2024Lyme disease is the most common wildlife-to-human transmitted disease reported in North America. The study of this disease requires an understanding of the ecology of...
Lyme disease is the most common wildlife-to-human transmitted disease reported in North America. The study of this disease requires an understanding of the ecology of the complex communities of ticks and host species involved in harboring and transmitting this disease. Much of the ecology of this system is well understood, such as the life cycle of ticks, and how hosts are able to support tick populations and serve as disease reservoirs, but there is much to be explored about how the population dynamics of different host species and communities impact disease risk to humans. In this study, we construct a stage-structured, empirically-informed model with host dynamics to investigate how host population dynamics can affect disease risk to humans. The model describes a tick population and a simplified community of three host species, where primary nymph host populations are made to fluctuate on an annual basis, as commonly observed in host populations. We tested the model under different environmental conditions to examine the effect of environment on the interactions of host dynamics and disease risk. Results show that allowing for host dynamics in the model reduces mean nymphal infection prevalence and increases the maximum annual prevalence of nymphal infection and the density of infected nymphs. Effects of host dynamics on disease measures of nymphal infection prevalence were nonlinear and patterns in the effect of dynamics on amplitude in nymphal infection prevalence varied across environmental conditions. These results highlight the importance of further study of the effect of community dynamics on disease risk. This will involve the construction of further theoretical models and collection of robust field data to inform these models. With a more complete understanding of disease dynamics we can begin to better determine how to predict and manage disease risk using these models.
Topics: Lyme Disease; Animals; Humans; Population Dynamics; Ixodes; Models, Theoretical; Ticks; Models, Biological; Borrelia burgdorferi; Host-Parasite Interactions; Nymph
PubMed: 38722910
DOI: 10.1371/journal.pone.0302874 -
Nature Communications May 2024The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and...
The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and symptom development. We characterized cytokine production capacity before and after antibiotic treatment in 1,060 Lyme borreliosis patients. We observed a negative correlation between antibody production and IL-10 responses, as well as increased IL-1Ra responses in patients with disseminated disease. Genome-wide mapping the cytokine production allowed us to identify 34 cytokine quantitative trait loci (cQTLs), with 31 novel ones. We pinpointed the causal variant at the TLR1-6-10 locus and validated the regulation of IL-1Ra responses at transcritpome level using an independent cohort. We found that cQTLs contribute to Lyme borreliosis susceptibility and are relevant to other immune-mediated diseases. Our findings improve the understanding of cytokine responses in Lyme borreliosis and provide a genetic map of immune function as an expanded resource.
Topics: Lyme Disease; Humans; Quantitative Trait Loci; Cytokines; Male; Female; Interleukin-10; Adult; Genome-Wide Association Study; Middle Aged; Interleukin 1 Receptor Antagonist Protein; Borrelia burgdorferi; Anti-Bacterial Agents; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Aged
PubMed: 38714679
DOI: 10.1038/s41467-024-47505-z -
Journal of Microbiological Methods May 2024Reliable detection of bacteria belonging to the Borrelia burgdorferi sensu lato species complex in vertebrate reservoirs, tick vectors, and patients is key to answer...
Reliable detection of bacteria belonging to the Borrelia burgdorferi sensu lato species complex in vertebrate reservoirs, tick vectors, and patients is key to answer questions regarding Lyme borreliosis epidemiology. Nevertheless, the description of characteristics of qPCRs for the detection of B. burgdorferi s. l. are often limited. This study covers the development and validation of two duplex taqman qPCR assays used to target four markers on the chromosome of genospecies of B. burgdorferi s. l. Analytical specificity was determined with a panel of spirochete strains. qPCR characteristics were specified using water or tick DNA spiked with controlled quantities of the targeted DNA sequences of B. afzelii, B. burgdorferi sensu stricto or B. bavariensis. The effectiveness of detection results was finally evaluated using DNA extracted from ticks and biopsies from mammals whose infectious status had been determined by other detection assays. The developed qPCR assays allow exclusive detection of B. burgdorferi s. l. with the exception of the M16 marker which also detect relapsing fever Borreliae. The limit of detection is between 10 and 40 copies per qPCR reaction depending on the sample type, the B. burgdorferi genospecies and the targeted marker. Detection tests performed on various kind of samples illustrated the accuracy and robustness of our qPCR assays. Within the defined limits, this multi-target qPCR method allows a versatile detection of B. burgdorferi s. l., regardless of the genospecies and the sample material analyzed, with a sensitivity that would be compatible with most applications and a reproducibility of 100% under measurement conditions of limits of detection, thereby limiting result ambiguities.
PubMed: 38714225
DOI: 10.1016/j.mimet.2024.106941 -
Journal of Vector Borne Diseases May 2024Lyme disease is a multisystemic disease caused by the bacteria in the Borrelia burgdorferi sensu lato complex, which is transmitted by ticks of Ixodes genus. Although...
BACKGROUND OBJECTIVES
Lyme disease is a multisystemic disease caused by the bacteria in the Borrelia burgdorferi sensu lato complex, which is transmitted by ticks of Ixodes genus. Although there are seroprevalence studies and case reports of Lyme disease from various regions in Turkey, there is no widespread epidemiological research. This study aimed to determine the frequency of Lyme disease in the cases followed-up after tick contact and to examine the isolated ticks to reveal tick population from Bolu province.
METHODS
The cases who applied to the emergency department due to tick contact between April and September 2020 were firstly evaluated in our infectious diseases and clinical microbiology outpatient clinic on the third day of exposure and antibodies against Lyme disease were investigated with IFA method to exclude the patients who were previously exposed to B. burgdrorferi. Thereafter, patients were requested to continue outpatient visits at the 1st and 3rd month control. At these controls serum samples were taken to study B. burgdorferi antibodies with ELISA method which was stored at -20°C until the study day.
RESULTS
Out of 123 patients who came to first control, 69 patients continued later to at least one of the two controls (either at first or third month). Of these 69 patients, only one (1.4%) was diagnosed with Lyme borreliosis according to clinical and laboratory features. Erythema migrans did not occur in any of the cases. Serum samples were assessed by ELISA method. Asymptomatic infection was detected in 22 cases (30.5%). In addition, we could obtain 46 ticks from our cases and two genera were identified. Forty-two (91.3%) were Ixodes spp, and two (4.3%) were Hyalomma spp.
INTERPRETATION CONCLUSION
In this study, which was carried out for the first time in the province of Bolu, it was concluded that the cases presenting with a history of tick contact were most frequently exposed to Ixodes spp ticks and the probability of developing Lyme borreliosis was low (1.4%) during the three-month follow-up. Further studies with a greater number of cases and more extended follow-up period are needed.
PubMed: 38712715
DOI: 10.4103/JVBD.JVBD_194_23 -
Journal of Central Nervous System... 2024'Definite Neuroborreliosis (NB)' is diagnosed with the presence of NB-specific symptoms, cerebrospinal fluid (CSF) pleocytosis and an elevated antibody index. However,...
BACKGROUND
'Definite Neuroborreliosis (NB)' is diagnosed with the presence of NB-specific symptoms, cerebrospinal fluid (CSF) pleocytosis and an elevated antibody index. However, some diagnostic uncertainties exist. The B-cell chemokine CXCL13 represents an emerging biomarker for the diagnosis and treatment of NB because its intrathecal concentration rises prior to the Borrelia antibody index and drops rapidly after antibiotic therapy. Nevertheless, due to lacking prospective data, a definite CXCL13 cut-off for the diagnosis of NB is still pending.
OBJECTIVE
Definition of a CSF CXCL13 cut-off for the diagnosis of acute and untreated NB in a prospective study setting.
DESIGN AND METHODS
This multicentre prospective study involved 6 neurological departments treating patients in the Lower Austria district (1.7 million inhabitants). The controls were patients scheduled for a spinal tap but not clinically diagnosed with NB. Demographic data, clinical characteristics and blood counts, as well as inflammatory CSF values and CSF CXCL13-concentration were analysed.
RESULTS
We recruited 440 adult patients, of whom 42 have been diagnosed as having an acute and untreated 'definite NB'. Three hundred ninety-eight patients were assigned to the control group. The median intrathecal CXCL13 concentration was 2384 pg/ml for patients with NB and 0 pg/ml for controls. The difference was highly statistically significant ( ≤ .001). A CSF CXCL13 cut-off of 271 pg/ml resulted in a sensitivity of 95.2% and a specificity of 97.2% for the confirmation or exclusion of NB.
CONCLUSION
Based on our results, we propose a CSF CXCL13 cut-off of 271 pg/ml with Euroimmun-Elisa for the diagnosis of acute and untreated NB. Due to its high sensitivity and specificity, CXCL13 is a strong candidate biomarker for routine NB assessment, especially in clinically unclear cases.
PubMed: 38706882
DOI: 10.1177/11795735241247026 -
Parasites & Vectors Apr 2024Ixodes inopinatus was described from Spain on the basis of morphology and partial sequencing of 16S ribosomal DNA. However, several studies suggested that morphological...
BACKGROUND
Ixodes inopinatus was described from Spain on the basis of morphology and partial sequencing of 16S ribosomal DNA. However, several studies suggested that morphological differences between I. inopinatus and Ixodes ricinus are minimal and that 16S rDNA lacks the power to distinguish the two species. Furthermore, nuclear and mitochondrial markers indicated evidence of hybridization between I. inopinatus and I. ricinus. In this study, we tested our hypothesis on tick dispersal from North Africa to Southern Europe and determined the prevalence of selected tick-borne pathogens (TBPs) in I. inopinatus, I. ricinus, and their hybrids.
METHODS
Ticks were collected in Italy and Algeria by flagging, identified by sequencing of partial TROSPA and COI genes, and screened for Borrelia burgdorferi s.l., B. miyamotoi, Rickettsia spp., and Anaplasma phagocytophilum by polymerase chain reaction and sequencing of specific markers.
RESULTS
Out of the 380 ticks, in Italy, 92 were I. ricinus, 3 were I. inopinatus, and 136 were hybrids of the two species. All 149 ticks from Algeria were I. inopinatus. Overall, 60% of ticks were positive for at least one TBP. Borrelia burgdorferi s.l. was detected in 19.5% of ticks, and it was significantly more prevalent in Ixodes ticks from Algeria than in ticks from Italy. Prevalence of Rickettsia spotted fever group (SFG) was 51.1%, with significantly greater prevalence in ticks from Algeria than in ticks from Italy. Borrelia miyamotoi and A. phagocytophilum were detected in low prevalence (0.9% and 5.2%, respectively) and only in ticks from Italy.
CONCLUSIONS
This study indicates that I. inopinatus is a dominant species in Algeria, while I. ricinus and hybrids were common in Italy. The higher prevalence of B. burgdorferi s.l. and Rickettsia SFG in I. inopinatus compared with that in I. ricinus might be due to geographical and ecological differences between these two tick species. The role of I. inopinatus in the epidemiology of TBPs needs further investigation in the Mediterranean Basin.
Topics: Animals; Ixodes; Italy; Algeria; Rickettsia; Tick-Borne Diseases; Prevalence; Borrelia; Anaplasma phagocytophilum; Female; Hybridization, Genetic; Male; RNA, Ribosomal, 16S; Borrelia burgdorferi
PubMed: 38685096
DOI: 10.1186/s13071-024-06271-z