Due to the functional inactivation of the gene encoding for the enzyme that is involved in the oligosaccharide galactose-α-1,3-galactose (α-Gal) synthesis, humans and Old-World primates are able to produce a large amount of antibodies against the glycan epitope. Apart from being involved in the hyperacute organ rejection in humans, anti-α-Gal antibodies have shown a protective effect against some pathogenic agents and an implication in the recently recognized tick-induced mammalian meat allergy. Conversely, non-primate mammals, including dogs, have the ability to synthetize α-Gal and, thus, their immune system is not expected to naturally generate the antibodies toward this self-antigen molecule. However, in the current study, we detected specific IgG, IgM, and IgE antibodies to α-Gal in sera of clinically healthy dogs by an indirect enzyme-linked immunosorbent assay (ELISA) for the first time. Furthermore, in a tick infestation experiment, we showed that bites of Ixodes ricinus induce the immune response to α-Gal in dogs and that the resulting antibodies (IgM) might be protective against Anaplasma phagocytophilum. These findings may help lead to a better understanding of the underlying mechanisms involved in mammalian meat allergy and tick-host-pathogen interactions, but they also open up the question about the possibility that dogs could develop an allergy to mammalian meat after tick bites, similar to that in humans.
- Publikační typ
- časopisecké články MeSH
The α-Gal syndrome (AGS) is a type of allergy characterized by an IgE antibody (Ab) response against the carbohydrate Galα1-3Galβ1-4GlcNAc-R (α-Gal), which is present in glycoproteins from tick saliva and tissues of non-catarrhine mammals. Recurrent tick bites induce high levels of anti-α-Gal IgE Abs that mediate delayed hypersensitivity to consumed red meat products in humans. This was the first evidence that tick glycoproteins play a major role in allergy development with the potential to cause fatal delayed anaphylaxis to α-Gal-containing foods and drugs and immediate anaphylaxis to tick bites. Initially, it was thought that the origin of tick-derived α-Gal was either residual blood meal mammalian glycoproteins containing α-Gal or tick gut bacteria producing this glycan. However, recently tick galactosyltransferases were shown to be involved in α-Gal synthesis with a role in tick and tick-borne pathogen life cycles. The tick-borne pathogen Anaplasma phagocytophilum increases the level of tick α-Gal, which potentially increases the risk of developing AGS after a bite by a pathogen-infected tick. Two mechanisms might explain the production of anti-α-Gal IgE Abs after tick bites. The first mechanism proposes that the α-Gal antigen on tick salivary proteins is presented to antigen-presenting cells and B-lymphocytes in the context of Th2 cell-mediated immunity induced by tick saliva. The second mechanism is based on the possibility that tick salivary prostaglandin E2 triggers Immunoglobulin class switching to anti-α-Gal IgE-producing B cells from preexisting mature B cells clones producing anti-α-Gal IgM and/or IgG. Importantly, blood group antigens influence the capacity of the immune system to produce anti-α-Gal Abs which in turn impacts individual susceptibility to AGS. The presence of blood type B reduces the capacity of the immune system to produce anti-α-Gal Abs, presumably due to tolerance to α-Gal, which is very similar in structure to blood group B antigen. Therefore, individuals with blood group B and reduced levels of anti-α-Gal Abs have lower risk to develop AGS. Specific immunity to tick α-Gal is linked to host immunity to tick bites. Basophil activation and release of histamine have been implicated in IgE-mediated acquired protective immunity to tick infestations and chronic itch. Basophil reactivity was also found to be higher in patients with AGS when compared to asymptomatic α-Gal sensitized individuals. In addition, host resistance to tick infestation is associated with resistance to tick-borne pathogen infection. Anti-α-Gal IgM and IgG Abs protect humans against vector-borne pathogens and blood group B individuals seem to be more susceptible to vector-borne diseases. The link between blood groups and anti-α-Gal immunity which in turn affects resistance to vector-borne pathogens and susceptibility to AGS, suggests a trade-off between susceptibility to AGS and protection to some infectious diseases. The understanding of the environmental and molecular drivers of the immune mechanisms involved in AGS is essential to developing tools for the diagnosis, control, and prevention of this growing health problem.
- MeSH
- alergeny imunologie MeSH
- anafylaxe etiologie MeSH
- červené maso MeSH
- genetická predispozice k nemoci MeSH
- hmyzí proteiny imunologie MeSH
- imunoglobulin E metabolismus MeSH
- interakce genů a prostředí MeSH
- klíšťata MeSH
- kousnutí klíštětem komplikace imunologie MeSH
- lidé MeSH
- potravinová alergie komplikace etiologie imunologie MeSH
- tvorba protilátek MeSH
- zkřížené reakce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The Subolesin/Akirin constitutes a good model for the study of functional evolution because these proteins have been conserved throughout the metazoan and play a role in the regulation of different biological processes. Here, we investigated the evolutionary history of Subolesin/Akirin with recent results on their structure, protein-protein interactions and function in different species to provide insights into the functional evolution of these regulatory proteins, and their potential as vaccine antigens for the control of ectoparasite infestations and pathogen infection. The results suggest that Subolesin/Akirin evolved conserving not only its sequence and structure, but also its function and role in cell interactome and regulome in response to pathogen infection and other biological processes. This functional conservation provides a platform for further characterization of the function of these regulatory proteins, and how their evolution can meet species-specific demands. Furthermore, the conserved functional evolution of Subolesin/Akirin correlates with the protective capacity shown by these proteins in vaccine formulations for the control of different arthropod and pathogen species. These results encourage further research to characterize the structure and function of these proteins, and to develop new vaccine formulations by combining Subolesin/Akirin with interacting proteins for the control of multiple ectoparasite infestations and pathogen infection.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Tick-borne diseases have become a world health concern, emerging with increasing incidence in recent decades. Spotted fever group (SFG) rickettsiae are tick-borne pathogens recognized as important agents of human tick-borne diseases worldwide. In this study, 88 adult ticks from the species Hyalomma anatolicum, Rhipicephalus annulatus, Rh. bursa, Rh. sanguineus sensu lato, and Rh. turanicus, were collected from farm ruminants in Lebanon, and SFG rickettsiae were molecularly identified and characterized in these ticks. The screening showed a prevalence of 68% for Rickettsia spp., including the species R. aeschlimannii, R. africae, R. massiliae and Candidatus R. barbariae, the latter considered an emerging member of the SFG rickettsiae. These findings contribute to a better knowledge of the distribution of these pathogens and demonstrate that SFG rickettsiae with public health relevance are found in ticks collected in Lebanon, where the widespread distribution of tick vectors and possible livestock animal hosts in contact with humans may favor transmission to humans. Few reports exist for some of the tick species identified here as being infected with SFG Rickettsia. Some of these tick species are proven vectors of the hosted rickettsiae, although this information is unknown for other of these species. Therefore, these results suggested further investigation on the vector competence of the tick species with unknown role in transmission of some of the pathogens identified in this study.
- MeSH
- farmy MeSH
- fylogeneze MeSH
- Ixodidae mikrobiologie MeSH
- koně MeSH
- kozy MeSH
- nemoci koní epidemiologie mikrobiologie MeSH
- nemoci koz epidemiologie mikrobiologie MeSH
- nemoci ovcí epidemiologie mikrobiologie MeSH
- nemoci skotu epidemiologie mikrobiologie MeSH
- ovce MeSH
- prevalence MeSH
- Rickettsia klasifikace fyziologie MeSH
- sekvenční analýza DNA MeSH
- skot MeSH
- skvrnité horečky epidemiologie mikrobiologie veterinární MeSH
- zvířata MeSH
- Check Tag
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Libanon epidemiologie MeSH
The carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) is produced in all mammals except for humans, apes and old world monkeys that lost the ability to synthetize this carbohydrate. Therefore, humans can produce high antibody titers against α-Gal. Anti-α-Gal IgE antibodies have been associated with tick-induced allergy (i.e. α-Gal syndrome) and anti-α-Gal IgG/IgM antibodies may be involved in protection against malaria, leishmaniasis and Chagas disease. The α-Gal on tick salivary proteins plays an important role in the etiology of the α-Gal syndrome. However, whether ticks are able to produce endogenous α-Gal remains currently unknown. In this study, the Ixodes scapularis genome was searched for galactosyltransferases and three genes were identified as potentially involved in the synthesis of α-Gal. Heterologous gene expression in α-Gal-negative cells and gene knockdown in ticks confirmed that these genes were involved in α-Gal synthesis and are essential for tick feeding. Furthermore, these genes were shown to play an important role in tick-pathogen interactions. Results suggested that tick cells increased α-Gal levels in response to Anaplasma phagocytophilum infection to control bacterial infection. These results provided the molecular basis of endogenous α-Gal production in ticks and suggested that tick galactosyltransferases are involved in vector development, tick-pathogen interactions and possibly the etiology of α-Gal syndrome in humans.
- MeSH
- alfa-galaktosidasa genetika metabolismus MeSH
- Anaplasma phagocytophilum patogenita MeSH
- ehrlichióza genetika metabolismus MeSH
- galaktosyltransferasy metabolismus MeSH
- genom genetika MeSH
- HL-60 buňky MeSH
- infekce přenášené vektorem MeSH
- interakce hostitele a patogenu genetika MeSH
- klíště mikrobiologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- proteiny členovců metabolismus MeSH
- sekvence aminokyselin MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
One of the major challenges in modern biology is the use of large omics datasets for the characterization of complex processes such as cell response to infection. These challenges are even bigger when analyses need to be performed for comparison of different species including model and non-model organisms. To address these challenges, the graph theory was applied to characterize the tick vector and human cell protein response to infection with Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis. A network of interacting proteins and cell processes clustered in biological pathways, and ranked with indexes representing the topology of the proteome was prepared. The results demonstrated that networks of functionally interacting proteins represented in both infected and uninfected cells can describe the complete set of host cell processes and metabolic pathways, providing a deeper view of the comparative host cell response to pathogen infection. The results demonstrated that changes in the tick proteome were driven by modifications in protein representation in response to A. phagocytophilum infection. Pathogen infection had a higher impact on tick than human proteome. Since most proteins were linked to several cell processes, the changes in protein representation affected simultaneously different biological pathways. The method allowed discerning cell processes that were affected by pathogen infection from those that remained unaffected. The results supported that human neutrophils but not tick cells limit pathogen infection through differential representation of ras-related proteins. This methodological approach could be applied to other host-pathogen models to identify host derived key proteins in response to infection that may be used to develop novel control strategies for arthropod-borne pathogens.
- MeSH
- Anaplasma phagocytophilum růst a vývoj MeSH
- anaplasmóza patologie MeSH
- biologické jevy MeSH
- buněčné linie MeSH
- členovci - vektory * MeSH
- interakce hostitele a patogenu * MeSH
- klíšťata MeSH
- lidé MeSH
- mapy interakcí proteinů MeSH
- proteiny analýza MeSH
- proteom analýza MeSH
- teoretické modely * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Malaria is a mosquito-borne disease affecting millions of people mainly in Sub-Saharan Africa, Asia and some South American countries. Drug resistance to first-line antimalarial drugs (e.g. chloroquine, sulfadoxine-pyrimethamine and artemisinin) is a major constrain in malaria control. Antimicrobial peptides (AMPs) have shown promising results in controlling Plasmodium spp. parasitemia in in vitro and in vivo models of infection. Defensins are AMPs that act primarily by disrupting the integrity of cell membranes of invasive microbes. We previously showed that defensins from the tick Ixodes ricinus inhibited significantly the growth of P. falciparum in vitro, a property that was conserved during evolution. Here, we tested the activity of three I. ricinus defensins against P. chabaudi in mice. A single dose of defensin (120 μl of 1 mg/ml solution) was administered intravenously to P. chabaudi-infected mice, and the parasitemia was followed for 24 h post-treatment. Defensin treatment inhibited significantly the replication (measured as increases in parasitemia) of P. chabaudi after 1 h and 12 h of treatment. Furthermore, defensin injection was not associated with toxicity. These results agreed with the previous report of antiplasmodial activity of tick defensins against P. falciparum in vitro and justify further studies for the use of tick defensins to control malaria.
- MeSH
- antimalarika aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- defensiny aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- intravenózní podání MeSH
- klíště chemie MeSH
- malárie farmakoterapie parazitologie MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- parazitemie farmakoterapie parazitologie MeSH
- Plasmodium účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Tick-borne infectious diseases and allergies are a growing problem worldwide. Tick bite allergy has been associated with the direct effect of immunoglobulin E (IgE) response to tick salivary antigens, or secondary to the induction of allergy to red meat consumption through IgE antibodies against the carbohydrate α-Gal (Gal α 1-3Gal β 1-(3)4GlcNAc-R). However, despite the growing burden of this pathology, the proteins associated with anaphylaxis to tick bite have not been characterized. To address this question, a comparative proteomics approach was used to characterize tick proteins producing an IgE antibody response in a healthy individual with record of tick bites, which had not resulted in any allergic reactions, and two patients with anaphylactic reactions to Rhipicephalus bursa or Hyalomma marginatum tick bites. Both patients and the healthy individual were red meat tolerant. The results supported a patient-specific IgE antibody response to tick species responsible for the anaphylaxis to tick bite. Both patients and the healthy individual serologically recognized tick proteins with and without α-Gal modifications, with proteins differentially recognized by patients but not control sera. These proteins could be used as potential antigens for diagnostics, treatment and prevention of tick bite-induced allergies.
- MeSH
- 2D gelová elektroforéza MeSH
- anafylaxe imunologie MeSH
- antigeny imunologie MeSH
- imunoglobulin E imunologie MeSH
- klíšťata imunologie MeSH
- kousnutí klíštětem komplikace imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- proteiny členovců imunologie MeSH
- proteomika MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The objective of this study was to screen and identify rickettsial organisms in ectoparasites collected from dogs in a shelter in Gomez Palacio, Durango, Mexico. One hundred dogs were inspected for ectoparasites. All the dogs were parasitized with Rhipicephalus sanguineus ticks, three with Heterodoxus spiniger lice and one with Ctenocephalides felis fleas. DNA was extracted from the ectoparasites found on each dog, and PCR with the primers for the Anaplasmataceae 16S rRNA and citrate synthase gltA genes were performed. Eight DNA samples obtained from ticks, three from lice and one from fleas were positive to 16S rRNA. Only one sample from C. felis and one from H. spiniger were positive to gltA. Sequence analysis of amplified products from C. felis showed identity to Rickettsia felis, Wolbachia pipientis, and Wolbachia spp., while a sequence from H. spiniger showed identity to Wolbachia spp. Herein we report the molecular detection of R. felis, W. pipientis, and Wolbachia spp. in C. felis and H. spiniger in northern Mexico. These results contribute to the knowledge of the microorganisms present in ectoparasites from dogs in Mexico.
- MeSH
- bakteriální RNA genetika MeSH
- bydlení zvířat MeSH
- DNA bakterií genetika MeSH
- druhová specificita MeSH
- fylogeneze MeSH
- infestace ektoparazity epidemiologie parazitologie veterinární MeSH
- klíšťata mikrobiologie MeSH
- nemoci psů epidemiologie parazitologie MeSH
- Phthiraptera mikrobiologie MeSH
- polymerázová řetězová reakce MeSH
- psi MeSH
- Rickettsia genetika izolace a purifikace MeSH
- RNA ribozomální 16S genetika MeSH
- sekvence nukleotidů MeSH
- Siphonaptera mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
