Tick galactosyltransferases are involved in alpha-Gal synthesis and play a role during Anaplasma phagocytophilum infection and Ixodes scapularis tick vector development

0497760 - BC 2019 RIV GB eng J - Článek v odborném periodiku
Cabezas Cruz, Alejandro - Espinosa, P. J. - Alberdi, P. - Šimo, L. - Valdés, James J. - Mateos-Hernández, L. - Contreras, M. - Villar Rayo, M. - de la Fuente, J.
Tick galactosyltransferases are involved in alpha-Gal synthesis and play a role during Anaplasma phagocytophilum infection and Ixodes scapularis tick vector development.
Scientific Reports. Roč. 8, September 21 (2018), č. článku 14224. ISSN 2045-2322. E-ISSN 2045-2322
Grant ostatní: Consejeria de Educacion, Cultura y Deportes, JCCM, Spain(ES) CCM17-PIC-036 (SBPLY/17/180501/000185)
Institucionální podpora: RVO:60077344
Klíčová slova: red meat allergy * multiple sequence alignment * human gb3/cd77 synthase * amino-acid * pathogen infection * metabolic pathways * immune-response * cell-lines * expression * identification
Obor OECD: Immunology
Impakt faktor: 4.011, rok: 2018
https://www.nature.com/articles/s41598-018-32664-z

The carbohydrate Gal alpha 1-3Gal beta 1-(3)4GlcNAc-R (alpha-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 alpha-Gal. Anti-alpha-Gal IgE antibodies have been associated with tick-induced allergy (i.e. alpha-Gal syndrome) and anti-alpha-Gal IgG/IgM antibodies may be involved in protection against malaria, leishmaniasis and Chagas disease. The alpha-Gal on tick salivary proteins plays an important role in the etiology of the alpha-Gal syndrome. However, whether ticks are able to produce endogenous alpha-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 alpha-Gal. Heterologous gene expression in alpha-Gal-negative cells and gene knockdown in ticks confirmed that these genes were involved in alpha-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 alpha-Gal levels in response to Anaplasma phagocytophilum infection to control bacterial infection. These results provided the molecular basis of endogenous alpha-Gal production in ticks and suggested that tick galactosyltransferases are involved in vector development, tick-pathogen interactions and possibly the etiology of alpha-Gal syndrome in humans.
Trvalý link: http://hdl.handle.net/11104/0290545