Allergic Reactions and Immunity in Response to Tick Salivary Biogenic Substances and Red Meat Consumption in the Zebrafish Model

Abstract

Ticks are arthropod ectoparasite vectors of pathogens and the cause of allergic reactions affecting human health worldwide. In humans, tick bites can induce high levels of immunoglobulin E antibodies against the carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) present in glycoproteins and glycolipids from tick saliva that mediate anaphylactic reactions known as the alpha-Gal syndrome (AGS) or red meat allergy. In this study, a new animal model was developed using zebrafish for the study of allergic reactions and the immune mechanisms in response to tick salivary biogenic substances and red meat consumption. The results showed allergic hemorrhagic anaphylactic-type reactions and abnormal behavior patterns likely in response to tick salivary toxic and anticoagulant biogenic compounds different from α-Gal. However, the results showed that only zebrafish previously exposed to tick saliva developed allergic reactions to red meat consumption with rapid desensitization and tolerance. These allergic reactions were associated with tissue-specific Toll-like receptor-mediated responses in types 1 and 2 T helper cells (T H 1 and T H 2) with a possible role for basophils in response to tick saliva. These results support previously proposed immune mechanisms triggering the AGS and provided evidence for new mechanisms also potentially involved in the AGS. These results support the use of the zebrafish animal model for the study of the AGS and other tick-borne allergies.

Vaccination with Alpha-Gal Protects Against Mycobacterial Infection in the Zebrafish Model of Tuberculosis

“…The experimental design used in this study addressed the protective efficacy of vaccination with α-Gal for the control of mycobacterial infection in the zebrafish model of tuberculosis using adjuvated (experiment 1; Figure 1 A) and not adjuvated (experiment 2; Figure 1 B) vaccine formulations. The rationale for using zebrafish is supported by constituting a validated model for tuberculosis [ 24 , 25 , 26 , 27 , 28 ] and the role of this species as an animal model for the study of the AGS [ 29 ]. The main objectives of the study were to characterize the effect of vaccination with α-Gal on mycobacterial infection and the immune mechanisms putatively involved in vaccine efficacy.…”

“…The previously shown role of antibodies against mycobacterial surface-exposed antigens in the control of tuberculosis [46] was also supported by results of our study. Zebrafish are α-Gal negative and have natural anti-α-Gal antibodies in response to gut microbiota [29]. Mycobacteria contain α-Gal on their surface, and therefore, antibodies against this antigen can opsonize M. marinum and promote Fc-receptor (FcR)-mediated phagocytosis and macrophage response with a higher effect in vaccinated zebrafish with higher anti-α-Gal antibody levels ( Figure 10).…”

“…Zebrafish is a model organism for the study of immune mechanisms and new effective vaccines and control strategies against tuberculosis [24][25][26][27][28]. Additionally, zebrafish do not produce α-Gal and were recently shown to reproduce some features of the human immune response to this molecule as a model for the study of the AGS [29]. The results of this study showed that vaccination with α-Gal protects against mycobacterial infection in the zebrafish model of tuberculosis to further advance the possibility of developing a pan-vaccine for the simultaneous control of major infectious diseases worldwide [30].…”

B Cell Responses in the Development of Mammalian Meat Allergy

“…These observations raise the possibility that signals through these receptors on innate and adaptive immune cells could be used to drive allergic sensitization to tick antigens and require further investigation. A new zebrafish animal model for the study of allergic reactions in response to tick saliva and red meat consumption has recently been developed that might be useful in this pursuit (157). Zebrafish do not express α-gal in their tissues and produce α-gal-specific IgM, similar to humans.…”

Immunity to Glycan α-Gal and Possibilities for the Control of COVID-19

“…Pathogens containing α-Gal on their surface include but are not limited to Plasmodium , Leishmania , Mycobacterium , Aspergillus , Trypanosoma , C retrovirus, porcine endogenous retrovirus, lymphocytic choriomeningitis virus, newcastle disease virus, sindbis virus, vesicular stomatitis virus, HIV, measles virus, paramyxovirus or vaccinia virus [ 2 , 3 ]. The proposed immune mechanisms associated with the AGS include TLR-mediated responses in both Th1 and Th2 cells and with a possible role for basophils in this process [ 4 ].…”