Mechanisms of immune evasion by Trypanosoma brucei.

Abstract

Trypanosoma brucei is the parasite responsible of causing both human (sleeping sickness) and animal (nagana) African trypanosomiasis, diseases of medical and veterinary importance. The infection in cattle has a major impact on African economy, which limits the production of milk and meat. The life cycle of these parasites extracellular alternate between the salivary glands of the insect transmitter (tsetse fly) and the blood of the vertebrate (mammal), presenting different morphological stages: procyclic, epimastigote, metacyclic forms in the invertebrate, long-slender trypomastigotes and short-stumpy forms in the vertebrate. The TAs are extracellular microorganisms that multiply in the blood and the lymphatic system and are constantly exposed to the attack of the the immune system of the mammalian host. During the step prior to the entry into the host, the metacyclic parasites express a dense cover formed by the Variant Surface Glycoprotein (VSG), after entering to the vertebrate host they transform into a morphology that stays in the blood (bloodstream). The most important mechanism for the maintenance in the bloodstream is the switch of VSG through which the parasites change his coat regularly and liberate the VSG expressed at this time, which allows the evasion of the attack of the immune system of the vertebrate host (specifically humoral response). In addition to all these events, this pathogens have generated an activation of M1 dependent of IFN-γ; express proteins of resistance to factors of human serum, for example, SRA (serum resistance antigen) and TgsGP (T. b. gambiense-specific glycoprotein); GIP-VSG produce the activation of NF-κB and MAPK pathways and the production of pro-inflammatory molecules (TNF-α, IL-6, IL-12p40, and GM-CSF) that with IFN-γ activated macrophages type M1, promotes a series of pathologies as tissue damage and encephalitis that provoke destruction in the Central Nervous System (CNS); these are just some of the factors that support the development of the infection in mammals. The African trypanosomes (AT) have learned to survive the attack of the defense system of vertebrates, through many years of carrying out a host-parasite interaction extremely complex and dynamic. Throughout the life cycle, these parasites re-programed your metabolism in order to benefit from the nutrients available in the environment. This abilities has allowed these escape magicians advance effectively and successfully in the development of immune system evasion mechanisms, allowing manipulating cellular and humoral responses, which implies a spectacular equilibrium in the vector/parasite/host relationship that allows their survival in the mammal and leads to a happy term their cycle of transmission.