Hyalomma marginatum is a prominent tick vector responsible for transmitting various pathogens, including the Crimean-Congo hemorrhagic fever virus (CCHFV), across Europe. This systematic review consolidates findings from 144 publications regarding the geographical distribution of H. marginatum and its associated pathogens. Significant populations have been identified primarily in Southern Europe and Balkan Peninsula, indicating a concerning trend. Additionally, climate change and migratory bird movements may facilitate its further dispersal, potentially leading to the establishment of H. marginatum in transalpine regions. Consequently, robust monitoring and surveillance strategies are essential to mitigate the public health and livestock threats posed by Hyalomma-borne diseases. Raising awareness and implementing preventive measures will be crucial in addressing the challenges associated with this tick vector.

• Keywords
• Crimean–Congo hemorrhagic fever virus, Hyalomma marginatum, Rickettsia, migratory birds, surveillance, tick distribution,
• MeSH
• Arachnid Vectors * virology   physiology   MeSH
• Ixodidae * virology   physiology   MeSH
• Animal Distribution MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Systematic Review MeSH
• Geographicals
• Europe epidemiology   MeSH

BACKGROUND: Alpha-Gal syndrome (AGS) is a tick-borne food allergy caused by IgE antibodies against the glycan galactose-alpha-1,3-galactose (α-Gal) present in glycoproteins and glycolipids from mammalian meat. To advance in the diagnosis and treatment of AGS, further research is needed to unravel the molecular and immune mechanisms underlying this syndrome. The objective of this study is the characterization of tick salivary components and proteins with and without α-Gal modifications involved in modulating human immune response against this carbohydrate. METHODS: Protein and α-Gal content were determined in tick saliva components, and proteins were identified by proteomics analysis of tick saliva fractions. Pathophysiological changes were recorded in the zebrafish (Danio rerio) model after exposure to distinct Ixodes ricinus tick salivary components. Serum samples were collected from zebrafish at day 8 of exposure to determine anti-α-Gal, anti-glycan, and anti-tick saliva protein IgM antibody titers by enzyme-linked immunosorbent assay (ELISA). RESULTS: Zebrafish treated with tick saliva and saliva protein fractions combined with non-protein fractions demonstrated significantly higher incidence of hemorrhagic type allergic reactions, abnormal behavioral patterns, or mortality when compared to the phosphate-buffered saline (PBS)-treated control group. The main tick salivary proteins identified in these fractions with possible functional implication in AGS were the secreted protein B7P208-salivary antigen p23 and metalloproteases. Anti-α-Gal and anti-tick salivary gland IgM antibody titers were significantly higher in distinct saliva protein fractions and deglycosylated saliva group when compared with PBS-treated controls. Anti-glycan antibodies showed group-related profiles. CONCLUSIONS: Results support the hypothesis that tick salivary biomolecules with and without α-Gal modifications are involved in modulating immune response against this carbohydrate.

• Keywords
• Allergy, Alpha-gal syndrome, Glycan, Tick, Zebrafish,
• MeSH
• Zebrafish metabolism   MeSH
• Galactose MeSH
• Immunoglobulin E MeSH
• Immunoglobulin M MeSH
• Ixodes * MeSH
• Tick Bites * MeSH
• Humans MeSH
• Food Hypersensitivity * etiology   MeSH
• Arthropod Proteins MeSH
• Mammals MeSH
• Saliva MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Galactose MeSH
• Immunoglobulin E MeSH
• Immunoglobulin M MeSH
• Arthropod Proteins MeSH

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.

• Keywords
• Ixodes ricinus, dog, immune response, pathogens, tick bite, α-Gal,
• Publication type
• Journal Article 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.

• Keywords
• IgE, food allergy, red meat allergy, ticks, α-Gal syndrome (AGS),
• MeSH
• Allergens immunology   MeSH
• Anaphylaxis etiology   MeSH
• Red Meat MeSH
• Genetic Predisposition to Disease MeSH
• Insect Proteins immunology   MeSH
• Immunoglobulin E metabolism   MeSH
• Gene-Environment Interaction MeSH
• Ticks MeSH
• Tick Bites complications   immunology   MeSH
• Humans MeSH
• Food Hypersensitivity complications   etiology   immunology   MeSH
• Antibody Formation MeSH
• Cross Reactions MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Allergens MeSH
• Insect Proteins MeSH
• Immunoglobulin E 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
• alpha-Galactosidase genetics   metabolism   MeSH
• Anaplasma phagocytophilum pathogenicity   MeSH
• Ehrlichiosis genetics   metabolism   MeSH
• Galactosyltransferases metabolism   MeSH
• Genome genetics   MeSH
• HL-60 Cells MeSH
• Disease Vectors MeSH
• Host-Pathogen Interactions genetics   MeSH
• Ixodes microbiology   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Arthropod Proteins metabolism   MeSH
• Amino Acid Sequence MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• alpha-Galactosidase MeSH
• Galactosyltransferases MeSH
• GLA protein, human MeSH Browser
• Arthropod Proteins MeSH