The role of Leishmania immune adherence reaction in human infection
PhD Thesis defense by Dario Cabañes Rodríguez at the Faculty of Veterinary Medicine of the Complutense University of Madrid
January 21st, 2016
The leishmanioses are vector-borne diseases caused by trypanosomatid protozoa of the genus Leishmania. This parasite has a heteroxenous life cycle, living as extracellular flagellated promastigote in the digestive tract of the insect vector and as obligate intracellular sessile amastigote within mononuclear phagocytes of vertebrate hosts. Leishmania is transmitted to susceptible hosts through the bite of infected sandflies of the genus Phlebotomus. Phlebotomine sandflies are telmophage diptera that feed from hematomas; infected females inoculate promastigotes into hematomas in host skin while probing for dermal capillaries. After blood contact, promastigotes are opsonized by host serum factors that trigger complement activation and C3 deposition on parasites. In primate blood, C3-opsonized promastigotes immune-adhere to erythrocytes and in non-primate mammalian blood, to platelets. Erythrocyte-bound promastigotes are subsequently shuttled to acceptor blood leukocytes and the C3-coated parasites are endocytosed by polymorphonuclear (PMN) phagocytes and monocytes. Inside phagolysosomes of permissive leukocytes, promastigotes differentiate to amastigotes and establish infection.
The objective of this thesis is to clarify the early reactions of human blood infection by Leishmania promastigotes which include, promastigote-erythrocyte IA reaction --> promastigote binding and internalization into granulocytes and monocytes, and promastigote triggering of cytokine expression and activation of the oxidative burst in infected leukocytes.
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