Recognition and invasion of human skin by Schistosoma mansoni cercariae: the key-role of L-arginine

Abstract

The attachment of Schistosoma mansoni cercariae to mammalian skin is specifically stimulated by L-arginine. As L-arginine is an unsuitable signal for a specific identification of mammalian skin we examined the following 5 hypotheses to explain the advantage of the cercarial sensitivity to L-arginine. (1) A Schistosoma infection lowered the arginine concentration in the serum of mice, and this could enable the cercariae to avoid attachments to already infected mice. However, the infection did not reduce the arginine concentration in the skin and the cercarial attachment responses to it. (2) Creeping cercariae showed chemotactic orientation specifically along increasing L-arginine gradients. L-arginine could act as a pheromone which could guide cercariae towards common penetration sites. However, the cercarial acetabular gland contents were not attractive and they did not (in contrast to previous reports) contain much arginine. (3) Schistosomula (transformed cercariae) could use L-arginine to produce nitric oxide (NO) for blood vessel dilation during their migration in the host. However, in vitro the transformed cercariae did not convert L-arginine into citrulline and NO. (4) Schistosomula could bind L-arginine from the surrounding tissues and so escape the cellular immune attack (which needs L-arginine as the precursor of NO). However, transformed cercariae bound no more L-arginine than L-serine and L-lysine. (5) Schistosomula, migrating parallel to the surface in the mammalian epidermis, are dependent on information on their position between the inner and the surface layers of the skin. In the mouse skin, they adjusted their body axis with the ventral side toward the deeper (arginine-residue rich) epidermis layers. When migrating in agar, they showed chemo-orientation toward serum, and D-glucose and L-arginine were the stimulating compounds therein. The burrowing schistosomula adjusted their body axis (as in the epidermis) with the ventral side toward the higher concentration of L-arginine and not of glucose. We argue that the sensitivity for L-arginine has its primary function in orientation within mammalian skin and in location of blood vessels.

Uptake of macromolecules by cercariae during skin penetration and transformation to schistosomula (Schistosoma mansoni)

“…Nature of the skin stimulus -The work of Haas et al (1997Haas et al ( , 2002 and Grabe and Haas (2004) provided insight as to the nature of the skin stimulus. At the epidermal surface, arginine, ceramides and linoleic acid stimulate Fig.…”

Plant-nematode interactions: environmental signals detected by the nematode’s chemosensory organs control changes in the surface cuticle and behaviour

“…These infective stages recognise their hosts via complex sequences of behavioural patterns with which they successfully respond to various environmental and host cues (Haas et al, 1997;Haas, 2003). After invasion animal parasites navigate through their host's tissues to their very specific microhabitats and some of these migrating parasitic stages can follow chemical gradients of skin and blood compounds (Haas et al, 2002). It is suggested that the high complexity, specificity and diversity of hostrecognition strategies devised by parasites are important determinants in the evolution of their life cycles.…”

Navigation within host tissues: cercariae orientate towards dark after penetration

“…Orientation of migrating schistosomula was studied using the W-chamber technique, modified from Haas et al (2002a). Briefly, the larvae penetrated agar in the central chamber (5·5 mm, height of agar 6 mm) of a three-armed cuvette.…”

“…In experiments with D. spathaceum it had to be more highly concentrated (0.5%) and contained 300 mosmol fishringer according to Haas (1974). Penetration and full transformation into schistosomula (as demonstrated by lectin staining, and in S. mansoni in addition by the Cercarienhu¨llen reaction; see Haas et al 2002a) was stimulated by a 1 mm layer of agar (pH 7.0, 5 mM phosphate buffer) containing a fatty acid, on the upper surface of the central agar block (50 lM linoleic acid in 0.25% agar for S. mansoni and T. ocellata, 50 lM linolenic acid in 0.5% agar for D. spathaceum). Both of the fatty acids used are natural penetration stimuli for the three trematode species (Shiff et al 1972;Haas and van de Roemer 1998;Haas et al 2002b).…”

“…Several of these organisms were swept away as they accidentally perforated the thin covering skin layers of their hosts. Recently, we showed that schistosomula of Schistosoma mansoni and T. ocellata probably obtain information on their position in the host's epidermis utilising concentration gradients of Larginine residues and glucose within the epidermis as orientation markers (Haas et al 2002a;Grabe and Haas, unpublished data). In the present study, we test the hypothesis that the parasites can also find their way towards deeper tissues and avoid a return to the skin surface when they use their photo-sensitivity.…”