The effects of protease inhibitors and sugars on the survival and development of the parasite Onchocerca ochengi in its natural intermediate host Simulium damnosum s.l.

Abstract

SummaryA range of protease inhibitors and carbohydrates were administered to the haemolymph of the vector Simulium damnosum s.l. to test for their effects on the success of an Onchocerca ochengi infection in vivo. We found that serine protease inhibitors led to a significant increase of parasite survival. Two sugars, d(+)-galactose and methyl--d-mannopyranoside, had the same effect. These effects are possibly due to the successful in vivo blocking of the two respective types of inducible immune molecules, the serine proteases and the carbohydrate binding lectins, both of which have been identified in simuliids.keywords onchocerciasis, insect immunity, proteases, lectins, S. damnosum, O. ochengi correspondence Dr

Is apoptosis involved in mechanisms to eliminate Onchocerca ochengi during Simulium damnosum s.l. immune response?

“…The other possible explanation is that z-VAD.fmk did not act on Onchocerca caspases, but may have blocked a haemolymph cysteine protease of S. damnosum s.l., thus leading to enhanced survival. This effect has been shown for the cysteine protease inhibitor E-64 (Hagen et al 1997b) as well as for an Onchocerca-derived inhibitor, onchocystatin (Kläger et al 1998).…”

“…Female S. damnosum s.l. were injected with 5 microfilariae of noncryopreserved microfilariae of O. ochengi and protease inhibitors as described previously (Hagen et al . 1997b).…”

“…Female S. damnosum s.l. were injected with 5 microfilariae of noncryopreserved microfilariae of O. ochengi and protease inhibitors as described previously (Hagen et al 1997b). The inhibitors used throughout the study were z-VAD.fmk (benzyloxycarbonyl-Val-Ala-Asp(OMe) fluoromethylketone, Enzyme Systems (USA) or boc-D.fmk (t-butyloxy carbonyl-Asp(OMe)fluoromethylketone, Enzyme Systems (USA), commonly used to block the activity of caspases, a distinct family of cysteine proteases which play a central role in apoptosis (Alnemri et al 1996;Whyte 1996).…”

“…1994a; 1997a), serine proteases (Hagen et al . 1995) and lectins, are important in controlling the survival and development of parasites (Hagen et al . 1997b).…”

“…(Denke & Bain 1978) and occurs throughout the cattle-breeding areas of Africa. Some of the compounds of the innate immune system such as prophenoloxidase (Hagen et al 1994a;1997a), serine proteases and lectins, are important in controlling the survival and development of parasites (Hagen et al 1997b). However, the question as to how exactly the parasite is killed still remains to be answered.…”