000079757 001__ 79757 000079757 005__ 20200716101500.0 000079757 0247_ $$2doi$$a10.3389/fimmu.2019.01210 000079757 0248_ $$2sideral$$a112681 000079757 037__ $$aART-2019-112681 000079757 041__ $$aeng 000079757 100__ $$aCabezas-Cruz, A. 000079757 245__ $$aEnvironmental and Molecular Drivers of the alpha-Gal Syndrome 000079757 260__ $$c2019 000079757 5060_ $$aAccess copy available to the general public$$fUnrestricted 000079757 5203_ $$aThe alpha-Gal syndrome (AGS) is a type of allergy characterized by an IgE antibody (Ab) response against the carbohydrate Gal alpha 1-3Gal beta 1-4GlcNAc-R (alpha-Gal), which is present in glycoproteins from tick saliva and tissues of non-catarrhine mammals. Recurrent tick bites induce high levels of anti-alpha-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 alpha-Gal-containing foods and drugs and immediate anaphylaxis to tick bites. Initially, it was thought that the origin of tick-derived alpha-Gal was either residual blood meal mammalian glycoproteins containing alpha-Gal or tick gut bacteria producing this glycan. However, recently tick galactosyltransferases were shown to be involved in alpha-Gal synthesis with a role in tick and tick-borne pathogen life cycles. The tick-borne pathogen Anaplasma phagocytophilum increases the level of tick alpha-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-alpha-Gal IgE Abs after tick bites. The first mechanism proposes that the alpha-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-alpha-Gal IgE-producing B cells from preexisting mature B cells clones producing anti-alpha-Gal IgM and/or IgG. Importantly, blood group antigens influence the capacity of the immune system to produce anti-alpha-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-alpha-Gal Abs, presumably due to tolerance to alpha-Gal, which is very similar in structure to blood group B antigen. Therefore, individuals with blood group B and reduced levels of anti-alpha-Gal Abs have lower risk to develop AGS. Specific immunity to tick alpha-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 alpha-Gal sensitized individuals. In addition, host resistance to tick infestation is associated with resistance to tick-borne pathogen infection. Anti-alpha-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-alpha-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. 000079757 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000079757 590__ $$a5.085$$b2019 000079757 591__ $$aIMMUNOLOGY$$b38 / 158 = 0.241$$c2019$$dQ1$$eT1 000079757 592__ $$a2.116$$b2019 000079757 593__ $$aImmunology and Allergy$$c2019$$dQ1 000079757 593__ $$aImmunology$$c2019$$dQ1 000079757 655_4 $$ainfo:eu-repo/semantics/review$$vinfo:eu-repo/semantics/publishedVersion 000079757 700__ $$aHodzic, A. 000079757 700__ $$aRoman-Carrasco, P. 000079757 700__ $$aMateos-Hernandez, L. 000079757 700__ $$aDuscher, G.G. 000079757 700__ $$aSinha, D.K. 000079757 700__ $$aHemmer, W. 000079757 700__ $$aSwoboda, I. 000079757 700__ $$0(orcid)0000-0001-7483-046X$$aEstrada-Pena, A.$$uUniversidad de Zaragoza 000079757 700__ $$ade la Fuente, J. 000079757 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal 000079757 773__ $$g10 (2019), 1210 [12 pp]$$pFront. immunol.$$tFRONTIERS IN IMMUNOLOGY$$x1664-3224 000079757 8564_ $$s602178$$uhttps://zaguan.unizar.es/record/79757/files/texto_completo.pdf$$yVersión publicada 000079757 8564_ $$s11218$$uhttps://zaguan.unizar.es/record/79757/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000079757 909CO $$ooai:zaguan.unizar.es:79757$$particulos$$pdriver 000079757 951__ $$a2020-07-16-09:12:30 000079757 980__ $$aARTICLE