Tick Bites Induce Anti-α-Gal Antibodies in Dogs
Status PubMed-not-MEDLINE Language English Country Switzerland Media electronic
Document type Journal Article
Grant support
CCM17-PIC-036 (SBPLY/17/180501/000185)
Consejería de Educación, Cultura y Deportes, JCCM, Spain
PubMed
31540167
PubMed Central
PMC6789585
DOI
10.3390/vaccines7030114
PII: vaccines7030114
Knihovny.cz E-resources
- Keywords
- Ixodes ricinus, dog, immune response, pathogens, tick bite, α-Gal,
- Publication type
- Journal Article 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.
SaBio Instituto de Investigación de Recursos Cinegéticos IREC CSIC UCLM JCCM 13005 Ciudad Real Spain
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Galili U., Shohet S.B., Kobrinm E., Stults C.L., Macher B.A. Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. J. Biol. Chem. 1988;263:17755–17762. PubMed
Galili U., Rachmilewitz E.A., Peleg A., Flechner I. A unique natural human IgG antibody with anti-alpha-galactosyl specificity. J. Exp. Med. 1984;160:1519–1531. doi: 10.1084/jem.160.5.1519. PubMed DOI PMC
Koike C., Uddin M., Wildman D.E., Gray E.A., Trucco M., Starzl T.E., Goodman M. Functionally important glycosyltransferase gain and loss during catarrhine primate emergence. Proc. Natl. Acad. Sci. USA. 2007;104:559–564. doi: 10.1073/pnas.0610012104. PubMed DOI PMC
Cabezas-Cruz A., Mateos-Hernández L., Pérez-Cruz M., Valdés J.J., Mera I.G.F., Villar M., de la Fuente J. Regulation of the immune response to α-Gal and vector-borne diseases. Trends Parasitol. 2015;31:470–476. doi: 10.1016/j.pt.2015.06.016. PubMed DOI
Cabezas-Cruz A., Hodžić A., Román-Carrasco P., Mateos-Hernández L., Duscher G.G., Sinha D.K., Hemmer W., Swoboda I., Estrada-Peña A., de la Fuente J. Environmental and molecular drivers of the α-Gal syndrome. Front. Immunol. 2019;10:1210. doi: 10.3389/fimmu.2019.01210. PubMed DOI PMC
Yilmaz B., Portugal S., Tran T.M., Gozzelino R., Ramos S., Gomes J., Regalado A., Cowan P.J., d’Apice A.J., Chong A.S., et al. Gut microbiota elicits a protective immune response against malaria transmission. Cell. 2014;159:1277–1289. doi: 10.1016/j.cell.2014.10.053. PubMed DOI PMC
Cabezas-Cruz A., de la Fuente J. Immunity to α-Gal: Toward a single-antigen pan-vaccine to control major infectious diseases. ACS Cent. Sci. 2017;3:1140–1142. doi: 10.1021/acscentsci.7b00517. PubMed DOI PMC
Sandrin M.S., McKenzie I.F. Galα(1,3)Gal, the major xenoantigen(s) recognised in pigs by human natural antibodies. Immunol. Rev. 1994;141:169–190. doi: 10.1111/j.1600-065X.1994.tb00877.x. PubMed DOI
van Nunen S.A., O’Connor K.S., Fernando S.L., Clarke L.R., Boyle R.X. An association between Ixodes holocyclus tick bite reactions and red meat allergy. Intern. Med. J. 2007;37(Suppl. 5):A132. PubMed
van Nunen S.A., O’Connor K.S., Clarke L.R., Boyle R.X., Fernando S.L. An association between tick bite reactions and red meat allergy in humans. Med. J. Aust. 2009;190:510–511. PubMed
Commins S.P., Satinover S.M., Hosen J., Mozena J., Borish L., Lewis B.D., Woodfolk J.A., Platts-Mills T.A. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. J. Allergy Clin. Immunol. 2009;123:426–433. doi: 10.1016/j.jaci.2008.10.052. PubMed DOI PMC
Cabezas-Cruz A., Espinosa P.J., Alberdi P., Šimo L., Valdés J.J., Mateos-Hernández L., Contreras M., Rayo M.V., de la Fuente J. Tick galactosyltransferases are involved in α-Gal synthesis and play a role during Anaplasma phagocytophilum infection and Ixodes scapularis tick vector development. Sci. Rep. 2018;8:14224. doi: 10.1038/s41598-018-32664-z. PubMed DOI PMC
Crispell G., Commins S.P., Archer-Hartman S.A., Choudhary S., Dharmarajan G., Azadi P., Karim S. Discovery of alpha-Gal-containing antigens in North American tick species believed to induce red meat allergy. Front. Immunol. 2019;10:1056. doi: 10.3389/fimmu.2019.01056. PubMed DOI PMC
Leschnik M., Feiler A., Duscher G.G., Joachim A. Effect of owner-controlled acaricidal treatment on tick infestation and immune response to tick-borne pathogens in naturally infested dogs from Eastern Austria. Parasit. Vectors. 2013;6:62. doi: 10.1186/1756-3305-6-62. PubMed DOI PMC
Mateos-Hernández L., Villar M., Moral A., Rodríguez C.G., Arias T.A., de la Osa V., Brito F.F., Fernández de Mera I.G., Alberdi P., Ruiz-Fons F., et al. Tick-host conflict: Immunoglobulin E antibodies to tick proteins in patients with anaphylaxis to tick bite. Oncotarget. 2017;8:20630–20644. doi: 10.18632/oncotarget.15243. PubMed DOI PMC
Apostolović D., Rodrigues R., Thomas P., Starkhammar M., Hamsten C., van Hage M. Immunoprofile of α-Gal- and B-antigen-specific responses differentiates red meat-allergic patients from healthy individuals. Allergy. 2018;73:1525–1531. doi: 10.1111/all.13400. PubMed DOI
Iniguez E., Schocker N.S., Subramaniam K., Portillo S., Montoya A.L., Al-Salem W.S., Torres C.L., Rodriguez F., Moreira O.C., Acosta-Serrano A., et al. An α-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by Leishmania major. PLoS Negl. Trop. Dis. 2017;11:e0006039. doi: 10.1371/journal.pntd.0006039. PubMed DOI PMC
Genomic Resources Development Consortium. Contreras M., de la Fuente J., Estrada-Peña A., Grubhoffer L., Tobes R. Transcriptome sequence divergence between Lyme disease tick vectors, Ixodes scapularis and Ixodes ricinus. Genomic Resources Notes. Mol. Ecol. Resour. 2014;14:1095. PubMed
Bell-Sakyi L., Zweygarth E., Blouin E.F., Gould E.A., Jongejan F. Tick cell lines: Tools for tick and tick-borne disease research. Trends Parasitol. 2007;23:450–457. doi: 10.1016/j.pt.2007.07.009. PubMed DOI
Bell-Sakyi L. Ehrlichia ruminantium grows in cell lines from four ixodid tick genera. J. Comp. Pathol. 2004;130:285–293. doi: 10.1016/j.jcpa.2003.12.002. PubMed DOI
Alberdi P., Ayllón N., Cabezas-Cruz A., Bell-Sakyi L., Zweygarth E., Stuen S., de la Fuente J. Infection of Ixodes spp. tick cells with different Anaplasma phagocytophilum isolates induces the inhibition of apoptotic cell death. Ticks Tick. Borne Dis. 2015;6:758–767. doi: 10.1016/j.ttbdis.2015.07.001. PubMed DOI
de la Fuente J., Ayoubi P., Blouin E.F., Almazán C., Naranjo V., Kocan K.M. Gene expression profiling of human promyelocytic cells in response to infection with Anaplasma phagocytophilum. Cell Microbiol. 2005;7:549–559. doi: 10.1111/j.1462-5822.2004.00485.x. PubMed DOI
Barbour A.G. Isolation and cultivation of Lyme disease spirochetes. Yale J. Biol. Med. 1984;57:521–525. PubMed PMC
Lis K., Najm N., de la Fuente J., de Mera I.F., Zweygarth E., Pfister K., Passos L.M. Use of Percoll gradients to purify Anaplasma marginale (Rickettsiales: Anaplasmataceae) from tick cell cultures. Ticks Tick Borne Dis. 2014;5:511–515. doi: 10.1016/j.ttbdis.2014.03.006. PubMed DOI
Hamsten C., Tran T.A.T., Starkhammar M., Brauner A., Commins S.P., Platts-Mills T.A.E., van Hage M. Red meat allergy in Sweden: Association with tick sensitization and B-negative blood groups. J. Allergy Clin. Immunol. 2013;132:1431–1434. doi: 10.1016/j.jaci.2013.07.050. PubMed DOI PMC
Rispens T., Derksen N.I., Commins S.P., Platts-Mills T.A., Aalberse R.C. IgE production to α-gal is accompanied by elevated levels of specific IgG1 antibodies and low amounts of IgE to blood group B. PLoS ONE. 2013;8:e55566. doi: 10.1371/journal.pone.0055566. PubMed DOI PMC
Hilger C., Fischer J., Swiontek K., Hentges F., Lehners C., Eberlein B., Morisset M., Biedermann T., Ollert M. Two galactose-α-1,3-galactose carrying peptidases from pork kidney mediate anaphylactogenic responses in delayed meat allergy. Allergy. 2016;71:711–719. doi: 10.1111/all.12835. PubMed DOI
Galili U. Anti-Gal: An abundant human natural antibody of multiple pathogeneses and clinical benefits. Immunology. 2013;140:1–11. doi: 10.1111/imm.12110. PubMed DOI PMC
Galili U., Matta K.L. Inhibition of anti-Gal IgG binding to porcine endothelial cells by synthetic oligosaccharides. Transplantation. 1996;62:356–362. doi: 10.1097/00007890-199607270-00018. PubMed DOI
Velasquez-Manoff M. What the Mystery of the Tick-Borne Meat Allergy could Reveal. [(accessed on 22 July 2019)];The New York Time Magazine. 2018 Available online: https://www.nytimes.com/2018/07/24/magazine/what-the-mystery-of-the-tick-borne-meat-allergy-could-reveal.html.
van Stijn C., van den Broek M., Vervelde L., Alvarez R.A., Cummings R.D., Tefsen B., van Die I. Vaccination-induced IgG response to Galα1-3GalNAc glycan epitopes in lambs protected against Haemonchus contortus challenge infection. Int. J. Parasitol. 2010;40:215–222. doi: 10.1016/j.ijpara.2009.07.009. PubMed DOI PMC
Rojas M., Restrepo-Jiménez P., Monsalve D.M., Pacheco Y., Acosta-Ampudia Y., Ramírez-Santana C., Leung P.S.C., Ansari A.A., Gershwin M.E., Anaya J.M. Molecular mimicry and autoimmunity. J. Autoimmun. 2018;95:100–123. doi: 10.1016/j.jaut.2018.10.012. PubMed DOI
Galili U., Buehler J., Shohet S.B., Macher B.A. The human natural anti-Gal IgG. III. The subtlety of immune tolerance in man as demonstrated by crossreactivity between natural anti-Gal and anti-B antibodies. J. Exp. Med. 1987;165:693–704. doi: 10.1084/jem.165.3.693. PubMed DOI PMC
Commins S.P., James H.R., Kelly L.A., Pochan S.L., Workman L.J., Perzanowski M.S., Kocan K.M., Fahy J.V., Nganga L.W., Ronmark E., et al. The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose. J. Allergy Clin. Immunol. 2011;127:1286–1293. doi: 10.1016/j.jaci.2011.02.019. PubMed DOI PMC
Cabezas-Cruz A., Mateos-Hernández L., Alberdi P., Villar M., Riveau G., Hermann E., Schacht A.M., Khalife J., Correia-Neves M., Gortazar C., et al. Effect of blood type on anti-α-Gal immunity and the incidence of infectious diseases. Exp. Mol. Med. 2017;49:e301. doi: 10.1038/emm.2016.164. PubMed DOI PMC