Immunobiology of African Trypanosomes: Need of Alternative Interventions

Abstract

Trypanosomiasis is one of the major parasitic diseases for which control is still far from reality. The vaccination approaches by using dominant surface proteins have not been successful, mainly due to antigenic variation of the parasite surface coat. On the other hand, the chemotherapeutic drugs in current use for the treatment of this disease are toxic and problems of resistance are increasing (see Kennedy (2004) and Legros et al. (2002)). Therefore, alternative approaches in both treatment and vaccination against trypanosomiasis are needed at this time. To be able to design and develop such alternatives, the biology of this parasite and the host response against the pathogen need to be studied. These two aspects of this disease with few examples of alternative approaches are discussed here.

Insect Stage-Specific Receptor Adenylate Cyclases Are Localized to Distinct Subdomains of the Trypanosoma brucei Flagellar Membrane

“…Sleeping sickness is recognized to be one of the world's most neglected diseases and poses a threat to 60 million people living in sub-Saharan Africa (1). The disease is fatal if left untreated, and therapeutic treatments are antiquated, difficult to administer, and increasingly ineffective (2,3). Due to its ability to infect livestock, T. brucei also hinders economic growth and agricultural development and as such represents a significant contributor to poverty in some of the most impoverished regions of the world (4).…”

Three Mitochondrial DNA Polymerases Are Essential for Kinetoplast DNA Replication and Survival of Bloodstream Form Trypanosoma brucei

“…The few current pharmacological options to treat HAT are hampered by high toxicity and the emergence of drug resistant parasites (1). Therefore, there is an urgent need for the development of new drugs.…”

Prolyl oligopeptidase-like deficient Trypanosoma evansi parasites are associated with reduced interleukin-10 concentrations in vivo and in vitro

“…The role of parasite prolyl oligopeptidases (POPs) in host physiology is closely linked to the catalysis of mammalian peptides during infection (Bastos et al 2005;2010;Kaszuba et al 2012;Fajtová et al 2015). Although POPs from different species share similar three-dimensional structures, divergences have been observed between species in terms of inhibition and the specificity of substrates that they hydrolyse (Kaszuba et al 2012;Bastos et al 2013).…”

“…Other parasite peptidases that have also been shown to inhibit Th1 responses during infection include a cysteine protease B from Leishmania mexicana and cathepsin B from Leishmania chagasi, that cleave human TGF-β, a cytokine that regulates IL-10 and thereby affecting immunosuppression (Somanna et al 2002;Buxbaum et al 2003;Buxbaum, 2015). In classical trypanosome infections, initial pro-inflammatory type I immune responses mediated by IFN-γ, nitric oxide (NO) and TNF are necessary for controlling the first wave of parasitaemia (Namangala et al 2001b;Stijlemans et al 2007;Baral, 2010). Interleukin 1b is also a strong mediator of inflammatory immune responses during T. brucei infections (Nyakundi et al 2002).…”