A study led by the National Center of Biotechnology (CNB-CSIC) and with the participation of the Institute in Advanced Chemistry of Catalonia (IQAC-CSIC), from the Spanish National Research Council (CSIC) describe a new function of CCR5 that would explain why the immune system does not function properly in individuals with CCR5 deficiencies who are facing certain viral infections or undergoing immunotherapy treatments. The work has been published in the Journal EMBO and shows the data obtained in an experimental vaccination model in mice, but also in CD4+ lymphocytes isolated from ccr5[delta]32 individuals.
The CCR5 receptor contributes to the mobility of different types of leukocytes, including the CD4+T lymphocytes necessary to generate powerful immune responses both at the cellular level and in the production of antibodies. Additionally, CCR5 is a necessary coreceptor for AIDS virus infection. The gene responsible for the production of CCR5 may have changes in its sequence (called polymorphisms) that affect its function. This is the case of the polymorphism known as CCR5[delta]32, present in 1% of the Spanish population, whose carriers are resistant to infection by the AIDS virus (HIV), but curiously they present more frequently lethal complications after infection with the Flu virus and the West Nile virus.
Raquel Blanco, CNB-CSIC researcher explains that “in mice that lack of CCR5, fewer cytokines and high affinity antibodies are produced in response to a second exposure to the antigen, that is to say, they do not have an efficient memory for long-term protection”. For Ana Martín Leal, co-author of the research, this is because “CCR5 is necessary for the T cell receptor (TCR) to form nanooligomers or nanoclusters, which favor the re-activation of memory CD4+ lymphocytes to low doses of antigen”. Furthermore, this same phenomenon was observed in CD4 lymphocytes isolated from ccr5[delta]32 individuals, suggesting that their memory responses may also be defective.
These new data could indicate that people carrying ccr5[delta]32 or others who affect CCR5 have poor immune responses against some viruses. They also open a new line of research to determine whether individuals with CCR5 polymorphisms generate effective protective antibody responses after being vaccinated against viruses, such as the flu or, in the future, the virus that causes COVID-19.
They have also participated in this work researchers from the Severo Ochoa Molecular Biology Center (CBMSO-CSIC-UAM), from the University of Freiburg, from the Higher Technical School of Engineering of the Comillas pontifical University of Madrid, from the Hospital of Valme, from the CIBER of liver and digestive diseases (CIBER-EDH) and neurodegenerative diseases (CIBERNED), from the Fundació ACE of Barcelona, and the Seville Bioinformatics Company CAEBI.
For more information:
CCR5 deficiency impairs CD4+ T cell memory responses and antigenic sensitivity through increased ceramide synthesis. Ana Martín-Leal, Raquel Blanco, Josefina Casas, María E. Sáez, Elena Rodríguez-Bovolenta, Itziar de Rojas, Carina Drechsler, Luis Miguel Real, Gemma Fabrias, Agustín Ruíz, Mario Castro, Wolfgang W.A. Schamel, Balbino Alarcón, Hisse M. van Santen, Santos Mañes. EMBO Journal 2020 e104749