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According to the results of research led by the Complutense University of Madrid (UCM), among the various strategies deployed by the Leishmania parasite to avoid tripping the human immune system is to trigger the SHP-1 protein.
The parasite does this by secreting a molecule capable of interacting with the Mincle receptor expressed by antigen-presenting dendritic cells that help induce T-lymphocytes to activate an immune reaction.
For dendritic cells to be able to present antigens to T-lymphocytes, they must also have been infected by the pathogen, or must acquire ‘remains’ from another infected cell. This latter process is called ‘cross-antigen presentation’ and requires specialized enzymatic machinery.”
Salvador Iborra, Researcher, Department of Immunology, Ophthalmology and ENT, UCM
Besides helping to control physiological cell processes like growth and proliferation, the newly discovered function of SHP-1 presented in Cellular Reports would be to limit the capacity of dendritic cells to cross-present antigens to be able to prevent autoimmune disorders, i.e. to stop lymphocytes from attacking healthy body tissue. The parasite masks its existence by activating this part of immune response management.
SHP-1 inhibitors, key to vaccination This study, conducted jointly with the Spanish National Centre for Cardiovascular Research (Spanish initials: CNIC) and the Champalimaud Centre for the Unknown in Lisbon, was conducted using genetically modified mice as an experimental version which lacks the Mincle receptor or the SHP-1 enzyme in dendritic cells.
“In addition, we’ve been able to check the usefulness of chemical compounds that block SHP-1 activation, such as NSC-87877. Among our results, we’ve shown that vaccination with dendritic cells treated with this inhibitor and loaded with parasite lysates induced a response in cytotoxic lymphocytes that protected the mice against infection”, Iborra reported.
Although vaccines against canine leishmaniasis exist for dogs, which act as reservoirs of the disease, there are still no vaccines against the disease in people, so”any progress in our knowledge of immunity to the parasite is useful to the development of an effective vaccine”, Iborra concluded.
Complutense University of Madrid
Khouili, S.C., et al. (2020) SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity. Cell Reports. doi.org/10.1016/j.celrep.2020.108468.