Vector-borne infectious diseases (220)Viral Infections and Vectors (111)Vector-Borne Animal Diseases (65)Insect symbiosis and bacterial influences (64)Insect and Pesticide Research (52)
Jakimovski D, Banović P, Mateska S, Stavrova M, Stamenkovska A, et al.
Ticks and tick-borne diseases •
Ticks and tick-borne pathogens (TBPs) pose an expanding health threat across Europe, yet few studies link tick infection data directly to human clinical outcomes. We conducted a prospective, cross-border "One Health" study in Serbia and North Macedonia to assess the prevalence, diversity, and potential transmission of TBPs from ticks to humans. A total of 133 tick-infested patients were enrolled at two healthcare centers (112 in Skopje, 26 in Novi Sad), and 135 ticks were collected from these individuals, alongside paired blood and serum samples. Overall, TBP DNA was detected in 66.6 % of ticks, with Rickettsia helvetica (25.9 %) and Rickettsia monacensis (12.5 %) were most common. Mixed infections occurred in 15 % of ticks, with up to three pathogens co-occurring. Other detected TBPs included Borrelia afzelii, Borrelia garinii, Borrelia lusitaniae, Anaplasma phagocytophilum, Babesia microti, and Babesia divergens. Four patients (3 %) had detectable pathogen DNA in blood, primarily Rickettsia spp. and Anaplasma spp., yet remained asymptomatic. Most common clinical outcome during the observation period was local hypersensitivity reaction (21.1 %), while α-Gal sensitization was detected in two cases. Phylogenetic analysis revealed Balkan Rickettsia and Borrelia strains were mostly identical to Western and Central European lineages, with a notable exception: a Bo. garinii strain from North Macedonia clustered with strains from Russia and China, indicating possible long-distance introduction. The present study demonstrates that human exposure to multiple TBPs is common and while asymptomatic bloodstream infections do occur, local hypersensitivity reactions are much more common.
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.
Banović P, Jakimovski D, Mijatović D, Bogdan I, Simin V, et al.
International journal of molecular sciences •
Tick-bite hypersensitivity encompasses a range of clinical manifestations, from localized allergic reactions to systemic conditions like alpha-gal syndrome (AGS), an IgE-mediated allergy to galactose-α-1,3-galactose (α-Gal). This study investigated the clinical, molecular, immunological, and genetic features of two hypersensitivity cases. Two cases were analyzed: a 30-year-old woman with fixed drug reaction (FDR)-like hypersensitivity and a 10-year-old girl with AGS exhibiting borderline α-Gal-specific IgE. Diagnostic methods included allergen-specific IgE quantification, HLA genotyping, histopathological examination, and the molecular detection of tick-borne pathogens using microfluidic PCR. Case I demonstrated histopathological features of chronic lymphocytic inflammation and eosinophilic infiltrates, with HLA-B13 and DRB113 alleles indicating genetic susceptibility to hypersensitivity, while histological findings suggested a localized FDR-like reaction. Case II exhibited borderline α-Gal-specific IgE, resolving completely with a mammalian-free diet. The presence of HLA-DRB101 and DQB1*05 in the second patient indicated a genetic predisposition to AGS and other atopic conditions. No infectious etiology was identified in either case. These findings emphasize the heterogeneity of tick-related hypersensitivity and the importance of HLA genotypes in susceptibility. Comprehensive molecular, immunological, and genetic profiling offers valuable insights into the mechanisms of hypersensitivity, supporting personalized approaches for the diagnosis and management of tick-induced allergic conditions.
Wu-Chuang A, Rojas A, Bernal C, Cardozo F, Valenzuela A, et al.
Frontiers in immunology •
Dengue has had a significant global health impact, with a dramatic increase in incidence over the past 50 years, affecting more than 100 countries. The absence of a specific treatment or widely applicable vaccine emphasizes the urgent need for innovative strategies. This perspective reevaluates current evidence supporting the concept of dual protection against the dengue virus (DENV) through natural antibodies (NAbs), particularly anti-α-Gal antibodies induced by the host's gut microbiome (GM). These anti-α-Gal antibodies serve a dual purpose. Firstly, they can directly identify DENV, as mosquito-derived viral particles have been observed to carry α-Gal, thereby providing a safeguard against human infections. Secondly, they possess the potential to impede virus development in the vector by interacting with the vector's microbiome and triggering infection-refractory states. The intricate interplay between human GM and NAbs on one side and DENV and vector microbiome on the other suggests a novel approach, using NAbs to directly target DENV and simultaneously disrupt vector microbiome to decrease pathogen transmission and vector competence, thereby blocking DENV transmission cycles.
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.
Juste RA, Ferreras-Colino E, de la Fuente J, Domínguez M, Risalde MA, et al.
Immunology •
Trained immunity (TRAIM) may be defined as a form of memory where innate immune cells such as monocytes, macrophages, dendritic and natural killer (NK) cells undergo an epigenetic reprogramming that enhances their primary defensive capabilities. Cross-pathogen protective TRAIM can be triggered in different hosts by exposure to live microbes or microbe-derived products such as heat-inactivated Mycobacterium bovis or with the glycan α-Gal to elicit protective responses against several pathogens. We review the TRAIM paradigm using two models representing distinct scales of immune sensitization: the whole bacterial cell and one of its building blocks, the polysaccharides or glycans. Observations point out to macrophage lytic capabilities and cytokine regulation as two key components in non-specific innate immune responses against infections. The study of the TRAIM response deserves attention to better characterize the evolution of host-pathogen cooperation both for identifying the aetiology of some diseases and for finding new therapeutic strategies. In this field, the zebrafish provides a convenient and complete biological system that could help to deepen in the knowledge of TRAIM-mediated mechanisms in pathogen-host interactions.
Bamgbose T, Alberdi P, Abdullahi IO, Inabo HI, Bello M, et al.
Scientific reports •
The possibility of exploiting the human immune response to glycan α-Gal for the control of multiple infectious diseases has been the objective of recent investigations. In this field of research, the strain of Escherichia coli O86:B7 has been at the forefront, but this Gram-negative microorganism presents a safety concern and therefore cannot be considered as a probiotic. To address this challenge, this study explored the identification of novel lactic acid bacteria with a safe history of use, producing α-Gal and having probiotic potential. The lactic acid bacteria were isolated from different traditionally fermented foods (kununn-zaki, kindirmo, and pulque) and were screened for the production of α-Gal and some specific probiotic potential indicators. The results showed that Ten (10) out of forty (40) [25%] of the tested lactic acid bacteria (LAB) produced α-Gal and were identified as Limosilactobacillus fermentum, Levilactobacillus brevis, Agrilactobacillus composti, Lacticaseibacillus paracasei, Leuconostoc mesenteroides and Weissella confusa. Four (4) LAB strains with highest levels of α-Gal were further selected for in vivo study using a mouse model (α1,3GT KO mice) to elucidate the immunological response to α-Gal. The level of anti-α-Gal IgG observed were not significant while the level of anti-α-Gal IgM was lower in comparison to the level elicited by E. coli O86:B7. We concluded that the lactic acid bacteria in this study producing α-Gal have potential probiotic capacity and can be further explored in α-Gal-focused research for both the prevention and treatment of various infectious diseases and probiotic development.
Thorel M, Mateos-Hernandez L, Mulot B, Azzouni MN, Hodžić A, et al.
Frontiers in immunology •
Aspergillosis is a fungal infection caused mainly by that often results in respiratory disease in birds. Aspergillosis is a major cause of morbidity and mortality in captive-bred penguin species. Currently, there is no registered vaccine to prevent aspergillosis. Recent research demonstrated that oral administration of gram-negative bacteria expressing high levels of galactose-α-1,3-galactose (α-Gal) modulates anti-α-Gal immunity and protects turkeys from clinical aspergillosis caused by experimental infection. The role of anti-α-Gal immunity in penguins has not been studied. Here, we tested the distribution of α-1,3-galactosyltransferase (α1,3GT) genes in the fecal microbiome of Humboldt penguins (). The occurrence of natural anti-α-Gal antibodies (Abs) in sera and eggs of healthy Humboldt penguins was also assessed. A trial was then conducted to test whether oral administration of Nissle, expressing high α-Gal levels, modulates anti-α-Gal immunity in a colony of Humboldt penguins. Animals in the vaccination and placebo groups were evaluated before the trial and followed for one year for aspergillosis detection using a diagnostic panel including computed tomography scans, capillary zone electrophoresis, 3-hydroxybutyrate levels, and anti- Abs. Anti-α-Gal Abs were detected in sera (IgM and IgY) and eggs (IgY) of healthy penguins. Microbiota analysis and functional predictions revealed the presence of α1,3GT genes in the microbiota of Humboldt penguins and other penguin species. A strong decrease in anti-α-Gal IgM levels was observed in all animals in the placebo group three months after vaccination protocol. This decrease was not observed in Nissle-treated penguins. After the vaccination protocol, we found a positive correlation between anti- IgY and anti-α-Gal IgY in the Nissle group, suggesting a correlation between the presence of the bacteria and these Abs. During the study period, three penguins exhibited respiratory signs consistent with aspergillosis. Two were from the placebo group whose symptoms resolved with specific treatments, while a single vaccinated individual developed fatal respiratory aspergillosis eight months after the trial. We conclude that Nissle represents a safe potential probiotic with a protective effect against aspergillosis in Humboldt penguins that deserves to be further explored for therapeutic uses in these animals.
Palinauskas V, Mateos-Hernandez L, Wu-Chuang A, de la Fuente J, Aželytė J, et al.
Frontiers in immunology •
Natural antibodies (Abs), produced in response to bacterial gut microbiota, drive resistance to infection in vertebrates. In natural systems, gut microbiota diversity is expected to shape the spectrum of natural Abs and resistance to parasites. This hypothesis has not been empirically tested. In this 'Hypothesis and Theory' paper, we propose that enteric microbiota diversity shapes the immune response to the carbohydrate α-Gal and resistance to avian malaria. We further propose that anti-α-Gal Abs are transmitted from mother to eggs for early malaria protection in chicks. Microbiota modulation by anti-α-Gal Abs is also proposed as a mechanism favoring the early colonization of bacterial taxa with α1,3-galactosyltransferase (α1,3GT) activity in the bird gut. Our preliminary data shows that bacterial α1,3GT genes are widely distributed in the gut microbiome of wild and domestic birds. We also showed that experimental infection with the avian malaria parasite induces anti-α-Gal Abs in bird sera. The bird-malaria-microbiota system allows combining field studies with infection and transmission experiments in laboratory animals to test the association between microbiota composition, anti-α-Gal Abs, and malaria infection in natural populations of wild birds. Understanding how the gut microbiome influences resistance to malaria can bring insights on how these mechanisms influence the prevalence of malaria parasites in juvenile birds and shape the host population dynamics.
Drug resistance has become a threat to global health, and new interventions are needed to control major infectious diseases. The composition of gut microbiota has been linked to human health and has been associated with severity of malaria. Fermented foods contribute to the community of healthy gut bacteria. Despite the studies connecting gut microbiota to the prevention of malaria transmission and severity, research on developing functional foods for the purpose of manipulating the gut microbiota for malaria control is limited. This review summarizes recent knowledge on the role of the gut microbiota in malaria prevention and treatment. This information should encourage the search for lactic acid bacteria expressing α-Gal and those that exhibit the desired immune stimulating properties for the development of functional food and probiotics for malaria control.
Villar M, Pacheco I, Mateos-Hernández L, Cabezas-Cruz A, Tabor AE, et al.
Expert review of proteomics •
Ticks are obligate hematophagous arthropods that synthesize the glycan Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) associated with the alpha-gal syndrome (AGS) or allergy to mammalian meat consumption. In this study, we used a proteomics approach to characterize tick proteins in salivary glands (sialome SG), secreted saliva (sialome SA) and with α-Gal modification (alphagalactome SG and SA) in model tick species associated with the AGS in the United States () and Australia (). Selected proteins reactive to sera (IgE) from patients with AGS were identified to advance in the identification of possible proteins associated with the AGS. For comparative analysis, the α-Gal content was measured in various tick species. The results confirmed that ticks produce proteins with α-Gal modifications and secreted into saliva during feeding. Proteins identified in tick alphagalactome SA by sera from patients with severe AGS symptomatology may constitute candidate disease biomarkers. The results support the presence of tick-derived proteins with α-Gal modifications in the saliva with potential implications in AGS and other disorders and protective capacity against tick infestations and pathogen infection. Future research should focus on the characterization of the function of tick glycoproteins with α-Gal in tick biology and AGS.