Ticks are parasites that feed on the blood of humans and animals, using it as their sole source of food. Due to their lifestyle, ticks at each life stage transmit various tick-borne pathogens while feeding on their hosts. Unlike mosquitoes - another important group of pathogen-transmitting arthropods - ticks can feed on the same host for prolonged periods, which underscores the importance of tick mechanisms that inhibit or reduce the host's defence mechanisms and, consequently, allow the transmission of pathogens. This unique tick-host-pathogen triangle requires the involvement of various tick molecules to mediate interactions with both host and pathogen molecules at multiple levels. This review highlights the glycan molecules identified in various tick species that can trigger an immune response and thus primarily affect the interaction with the host. As the enzymes involved in Golgi-mediated glycan maturation differ between ticks, insects, and their vertebrate hosts, these differences contribute to the glycan profiles observed in ticks. These differences in glycan structures influence the interactions ticks have with their hosts and pathogens. On one hand, they may participate in molecular mimicry and mechanisms that lower the host's immune reaction, blood clotting, and other defence mechanisms due to their different structures, but on the other hand they may also trigger the host's defence mechanisms, such as participating in delayed red meat allergy and facilitating the transmission of pathogens. Tick glycobiology remains largely unexplored and deserves more attention, especially considering the potential of glycans and glycoproteins as targets for anti-tick vaccines.
Mateos-Hernandez L, Wu-Chuang A, Maitre A, Rego ROM, Abuin-Denis L, et al.
Ticks and tick-borne diseases •
The gut microbiome undergoes natural selection pressure, likely because it can affect infection resistance by stimulating natural antibody (NAb) production, notably against the glycan Galα1-3Galβ1-4GlcNAc-R (α-Gal). In our study, we explored whether particular glycans, such as α-Gal, from specific host microbiota components could trigger NAbs that, once ingested by Ixodes ricinus ticks during the blood meal, are capable of cross-reacting with bacterial strains in the tick microbiota that share these glycans. Such interactions might alter the tick microbiota and reduce Borrelia afzelii colonization in ticks. When mice were orally administered various Escherichia coli strains, it triggered the stimulation of NAbs and resulted in strain-specific alterations in the tick microbiota. These changes effectively decreased Borrelia colonization in the tick vector. Additionally, vaccination with the glycan α-Gal induced notable shifts in the tick microbiota and similarly reduced Borrelia colonization. Reduced Borrelia colonization was associated with shifts in bacterial diversity, abundance, and microbial network properties. The study provides evidence that natural mechanisms, such as the production of NAb in response to the host gut microbiome, can modulate the microbiota of disease vectors and reduce pathogen colonization within the vector. These findings offer new insights into potential strategies for reducing the transmission of vector-borne diseases through modulation of the host gut microbiome.
Contreras M, Vaz-Rodrigues R, Mazuecos L, Villar M, Artigas-Jerónimo S, et al.
Parasites & vectors •
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. 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). 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. Results support the hypothesis that tick salivary biomolecules with and without α-Gal modifications are involved in modulating immune response against this carbohydrate.
Cabezas-Cruz A, Espinosa PJ, Alberdi P, Šimo L, Valdés JJ, et al.
Scientific reports •
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.
Mateos-Hernández L, Villar M, Moral A, Rodríguez CG, Arias TA, et al.
Oncotarget •
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.
Cabezas-Cruz A, Mateos-Hernández L, Chmelař J, Villar M, de la Fuente J
Trends in parasitology •
Tick-induced allergy to red meat is associated with anti-α-Gal IgE antibody levels. We propose that tick salivary prostaglandin E2 triggers antibody class switching in mature B cells, increasing the levels of anti-α-Gal IgE antibodies. Immune tolerance to α-Gal in blood type B individuals might reduce the risk to this allergy.
