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

Abstract

The protozoan parasite Trypanosoma evansi is responsible for causing Surra in a variety of mammalian hosts over a wide geographical area. In the absence of an effective vaccine and increasing resistance to current chemotherapeutic agents, peptidases from the S9 prolyl oligopeptidase family have been identified as potential drug and vaccine targets. In order to understand the function of these peptidases during infection, three null mutant clones for prolyl oligopeptidase (Δpop), prolyl oligopeptidase-like (Δpop-like) and oligopeptidase B (Δopb) were generated in T. evansi RoTat 1.2 parasites and used for infection of mice. Mice inoculated with T. evansi Δpop-like mutants were able to survive longer than other groups of mice inoculated with Δpop, Δopb mutants or wild-type parasites. The regression analysis of plasma from mice-infected over time using Δpop-like mutants showed stable levels of interleukin-10 (IL-10) (non-significant slope, P = 0·171) and declining IL-1b levels (negative slope, P = 0·04) when compared with the wild-type control that demonstrated increasing levels of IL-10 and IL1b (P < 0·01 for both). Further analysis using mouse spleen cells in an in vitro 24 h incubation assay revealed that the percentage of IL-10 producing CD3 positive cells display significantly lower values when incubated with Δpop-like parasites than the wild-type clone (P = 0·002). These results suggest that prolyl oligopeptidase-like peptidase may play a role in immune responses during T. evansi infections by affecting interleukin concentrations in the host. IntroductionThe mechanically transmitted protozoan parasite Trypanosoma evansi, a causative agent of the disease called Surra, is geographically the most widely distributed member of the genus Trypanosoma and infects the widest range of mammalian hosts, including buffaloes, camels, cattle, pigs, dogs, horses and goats (Holland et al. 2003;Dargantes et al. 2009;Desquesnes et al. 2013;Salah et al. 2015). Trypanosoma evansi parasites are transmitted by bloodsucking flies (Tabanus and Stomoxys spp.) (Hoare, 1972;Sumba et al. 1998) and also by vampire bats in South America (Hoare, 1965). Unlike T. congolense, a haemoparasite that is strictly restricted to the host blood vessels, the absence of T. evansi in the bloodstream can still result in pathogenic symptoms from parasites that have invaded host tissue (Holland et al. 2003;Desquesnes et al. 2013). The symptoms associated with T. evansi infections differ depending on the susceptibility of the infected host and include anaemia, fever, loss of weight and productivity as well as abortion (Vickerman et al. 1993;Desquesnes et al. 2013). In classical trypanosome infections, most of the symptoms emerge when the host immune system targets infective parasites. Parasites that die as a result of the host immune response release biologically active products that have been associated with disease symptoms (Taylor and Authié, 2004;Antoine-Moussiaux et al. 2009). These toxins include enzymes such as trypanosome peptidases that hyd...

Prolyl Oligopeptidase From Leishmania infantum: Biochemical Characterization and Involvement in Macrophage Infection

“…This signalization was proposed as a trypanosome quorum sensing mechanism to control virulence and infection spread (Rojas et al, 2019). In Trypanosoma evansi infections, mice inoculated with a null mutant clone for a POP-like gene were able to survive longer than those inoculated with wild-type parasites (Kangethe et al, 2017). As well, Schistosoma mansoni POP may contribute to parasite survival by cleaving host bioactive peptides (Fajtová et al, 2015).…”