Effect of Leishmania immune complexes on the macrophage function
An immune complex (IC) is the combination of an antigen with an antibody. When produced in excess, ICs may be deposited in the walls of blood vessels, causing inflammation. ICs are implicated in the pathogenesis of multiple veterinary autoimmune and infectious diseases; examples are lupus, arthritis, ehrlichiosis, Lyme disease, canine adenovirus, dirofilariasis and leishmaniasis. We study canine visceral leishmaniasis, that is a progressive systemic disease caused by the parasite Leishmania infantum (chagasi). Visceral leishmaniasis is also a zoonosis: dogs are considered the reservoir in many areas of the world. Infected dogs produce high amounts of immunoglobulins (Ig). Ig-coated parasites form ICs that are internalized by macrophages (Mø) via Fc receptors. It is now known that the distinct engagement of different Fc receptors can influence the outcome of the immune response towards either inflammation or suppression. Dogs and humans with visceral leishmaniasis have decreased lymphocyte responses; infected humans have increased levels of circulating IL-10. Mouse studies have revealed that ICs formed following Leishmania infection induced the generation of inhibitory Mø that produce IL-10 to promote immunosuppression and disease progression. The objective of this project is to study whether the role of circulating immune complexes in canine leishmaniasis.