- Email: [email protected]
Comparison of skin invasion among three major species of Schistosoma
Update
TRENDS in Parasitology
Vol.21 No.5 May 2005
Research Focus
Comparison of skin invasion among three major species of Schistosoma Yi-Xun He, Bernard Salafsky and Kalyanasundaram Ramaswamy Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL 61107, USA
A comparison of the host-finding behavior, mode of skin invasion and skin-migratory patterns of the three major schistosomes of humans reveals major differences. Among the three species, Schistosoma japonicum is remarkable at conserving energy during the host-finding process, and exhibiting swift migration through the skin to reach the predilection site sooner and mature earlier compared with Schistosoma mansoni and Schistosoma haematobium. In this article, we summarize and compare the penetration and migratory behavior of schistosomula of the three major human schistosomes through mouse and human skin. Skin-penetration behavior Human schistosomiasis infections occur when cercariae penetrate intact skin. Current knowledge of the skinpenetration behavior of schistosome cercariae is based mainly on studies using mouse models, and O90% of these studies used Schistosoma mansoni as the model [1–4]. The findings from these studies have been generalized to other species of schistosome. Unfortunately, the migratory behavior of cercariae through human skin has not been studied extensively [5,6]. Several recent publications in Trends in Parasitology [6–10] have dealt with the skinpenetration behavior of S. mansoni, but there is still a large gap in the understanding of the host–parasite relationships of Schistosoma japonicum and Schistosoma haematobium in the skin. Disparate but important data regarding S. japonicum and S. haematobium have been published in non-English peer-reviewed journals [11]. Host finding Cercariae of the three major schistosome species show marked differences in their migratory behavior through water before entering mammalian skin. Cercariae of S. japonicum swim to the top layer of water and rest there by floating with their ventral sides up and their tails bent down dorsally [11]. This behavior maximizes their chance of finding the host, while expending minimum energy and potentially prolonging their lives. Cercariae of S. mansoni and S. haematobium, however, are distributed throughout the body of water and rest only transiently, with their tails pointed towards the water surface and their bodies oriented down. Host finding by schistosome cercariae is a complex multistep procedure in which cercariae respond to Corresponding author: Ramaswamy, K. ([email protected]). Available online 18 March 2005 www.sciencedirect.com
thermostatic gradients or chemical cues from the host that eventually orient them to host skin [12]. Cercariae of S. haematobium are more sensitive to thermal gradients than to chemical cues, whereas S. mansoni relies largely on chemical signals to identify the host [13,14]. However, chemical cues seem to have no major role in the hostfinding behavior of S. japonicum cercariae [12]. Cercariae of S. japonicum can attach passively to the skin while the host pulls the body out of the water, thus enabling the cercariae to expend minimum energy in this process (Y-X. He, unpublished). Following this, thermal gradient seems to have a role in their creeping action onto the skin [4,12]. Thus, the three major schistosomes differ slightly in their host-finding behavior.
Cercarial penetration of host skin After the host is identified, the cercariae attach to the epidermis using their ventral suckers. The anterior part of schistosome cercariae has a specialized head organ that can stretch out and retract slightly [15] (Figure 1a). This head organ is used initially to find a suitable place for invasion [4]. The apex of the head organ forms a slightly elevated disc-like area at which the external opening of the acetabular gland ducts is present [16]. The secretions from these glands are sticky and are released into the microenvironment in large quantities after stimulation [11] (Figure 1b). They are rich in elastase enzymes (cercarial proteases) that assist skin penetration [17–19]. Substantial information is available regarding the nature and function of the cercarial enzymes in S. mansoni [9]. However, only limited information is available about the cercarial enzymes of S. japonicum, especially considering that S. japonicum cercariae differ in their host spectrum and migratory behavior. It has been shown that both gelatin and starch-agar film substrates are lysed by cercariae of S. japonicum following incubation at 378C for 7 h [15,17] (Figure 1c). This suggests that both protease and polysaccharase enzyme activities are present in the secretions from S. japonicum cercariae. The mechanical movement of the head organ, and the protease enzymes secreted from the head and acetabular glands help the initial forced entry of the parasite into the skin [9,15,18,19]. Secretions from the head gland are also important for subsequent migration of the parasite through the basement membrane and blood-vessel wall [8]. Typically, cercariae and schistosomula enter the stratum corneum of the skin at a 408 angle [4,15], not vertically as had been reported previously [1]. Similarly,
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Figure 1. (a) Scanning electron micrograph of the head organ of a Schistosoma japonicum cercaria. Scale barZ2 mm. Image reproduced, with permission, from Ref. [15]. (b) Three cercariae of S. japonicum are seen discharging copious amounts of their head and/or acetabular gland contents. Image reproduced, with permission, from Ref. [11]. (c) A living cercaria of S. japonicum was incubated in gelatin film at 378C for 7 h. Note the prominent area of gelatin lysed around the anterior end of the cercaria. Image reproduced, with permission, from Ref. [15]. Scale bars in (b,c)Z100 mm.
cercariae of all three major schistosomes can penetrate and enter mouse or human skin through any skin surface, irrespective of hair follicles or sebaceous glands [4,5,15]. Skin-migratory patterns Although entry of cercariae into host skin occurs within minutes, there seem to be major differences in the skinmigratory behavior of the three major schistosomes. During the initial 2 h after exposure, O50% of S. japonicum schistosomula were present in the dermis of both human and mouse. By 24 h, however, nearly 100% of the parasites had left the mouse epidermis [4]. The migratory pattern of S. japonicum through human skin is similar to that through mouse skin except for a slight delay in migration through human epidermis. Nevertheless, schistosomula of S. japonicum were seen inside the dermal blood vessels of humans as early as 2 h after exposure to infection [5] (Figure 2a) and inside the hypodermal vessels of mice within 24 h after infection [15] (Figure 2b). Entry of the schistosomula into blood vessels also seems to occur in an oblique fashion, virtually ripping through the vessel wall. Faster migration of S. japonicum through host tissue potentially enables it to reach the predilection site sooner than S. mansoni and S. haematobium, and to mature early. It has been reported that S. japonicum oviposition occurs within 24–27 days [20],
(a)
(b)
whereas it takes 30–35 days and 60–63 days for S. mansoni and S. haematobium, respectively [21]. Migratory patterns of S. mansoni through host skin seem to be different from those of S. japonicum. Eight hours after exposure to infection, 94% of the schistosomula of S. mansoni were present in the epidermis of human skin [5], whereas only 59% were present in mouse skin epidermis. When examined 24 h after infection, nearly 89% of the S. mansoni schistosomula were still in the epidermis of human skin [5]. In fact, live schistosomula were present in human skin epidermis 96 h after infection. The average thickness of mouse abdominal skin epidermis is 0.037 mm (ranging from 0.021 mm to 0.046 mm), whereas the average thickness of human foreskin epidermis is 0.143 mm (ranging from 0.121 mm to 0.164 mm). Thus, the thickness of human epidermis is approximately four times that of mouse epidermis. This might explain the initial slower migration of S. mansoni schistosomula through human epidermis. Despite this slower migration, the majority of the schistosomula reaches the dermis within 48 h after infection in both mouse (68%) and human (60%) skin. Within 72 h after infection, 90% (mouse skin) and 71% (human skin) of schistosomula were present in the dermis, mostly close to blood vessels [5] (Figure 2c). The migratory pattern of S. haematobium schistosomula through human [5] and hamster [22] skin seems to
(c)
Figure 2. (a) Human skin 2 h after exposure to 150 cercariae of Schistosoma japonicum. Note the presence of a schistosomulum (arrowed) inside the dermal vessel. Image reproduced, with permission, from Ref. [5]. (b) Mouse skin 24 h after infection with 300 cercariae of S. japonicum. A schistosomulum is seen ripping through the vessel wall of a hypodermal blood vessel. Note that the parasite is entering the vessel at an angle. Image reproduced, with permission, from Ref. [15]. Scale bars in (a,b)Z100 mm. (c) Human skin 72 h after infection with 150 cercariae of Schistosoma mansoni. Note the presence of a schistosomulum (arrowed) close to the blood vessel. Scale barZ50 mm. Image reproduced, with permission, from Ref. [5]. www.sciencedirect.com
Update
TRENDS in Parasitology
be similar to that of S. mansoni. More than 93% of S. haematobium schistosomula were seen only in the epidermis 8 h after exposure of human skin to infection [5]. Approximately 48–72 h after infection, the majority of S. haematobium schistosomula was seen entering the dermis and, within 72 h, several of these schistosomula were seen close to the blood vessels. Similar findings were observed in hamster skin [22]. The presence of several schistosomula within the dermal or hypodermal blood vessels suggests that all three major human schistosomes can use blood as their major route of migration from the skin to the lungs. However, schistosomula of S. japonicum are also occasionally seen inside lymphatic vessels in human skin (Y-X. He, unpublished), as has been reported for S. mansoni in mice [23] and S. haematobium in gerbils [24]. Thus, schistosomula of S. mansoni and S. haematobium take nearly three days to complete their skin migration, whereas those of S. japonicum complete their migration in just one day [5,17], and peak numbers of S. japonicum schistosomula arrive in the lungs approximately three days after infection [25]. Not all cercariae that attempt to penetrate the skin make it: some die in the process [26–28]. Interestingly, the death of newly transformed schistosomula during skin penetration was substantially lower for S. japonicum (7%) [26] than for S. mansoni (28–43%) [27] or S. haematobium (30%) [28]. Thus, overall, S. japonicum has better survival strategies, which might explain its ability to establish itself in a wide spectrum of hosts [29]. Future perspectives A comparison of the host-finding, skin-penetration and migratory behaviors of the three major species of human schistosome reveals major differences. Migratory behavior of the schistosomula of S. japonicum in human and mouse skin is virtually the same. However, the other two species of schistosome seem to migrate more slowly, especially in human skin. The schistosomula of S. japonicum complete their skin migration in one day, whereas those of S. mansoni and S. haematobium take three to five days to do so. The factors that help the schistosomula of S. japonicum to migrate faster through the skin and to become established in the host sooner are unknown. As more data about the functional proteomics of these parasites become available, a complete picture of the molecular mechanism of skin penetration will emerge and will help to identify a potential target for drug or vaccine development against skin-penetrating or lung-stage parasites. Acknowledgements Financial support was provided by NIH grant AI39066.
References 1 Gordon, R.M. and Griffiths, R.B. (1951) Observations on the means by which the cercariae of Schistosoma mansoni penetrate mammalian skin, together with an account of certain morphological changes observed in the newly penetrated larvae. Ann. Trop. Med. Parasitol. 45, 227–243 2 Stirewalt, M.A. and Dorsey, C.H. (1974) Schistosoma mansoni: cercarial penetration of host epidermis at the ultrastructural level. Exp. Parasitol. 35, 1–15 www.sciencedirect.com
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3 Wheater, P.R. and Wilson, R.A. (1979) Schistosoma mansoni: a histological study of migration in the laboratory mouse. Parasitology 79, 49–62 4 He, Y.X. et al. (1989) Observations on the mode of epidermal penetration of Schistosoma japonicum cercariae. Acta Zool. Sin. 35, 66–72 5 He, Y.X. et al. (2002) Schistosoma mansoni, S. haematobium, and S. japonicum: early events associated with penetration and migration of schistosomula through human skin. Exp. Parasitol. 102, 99–108 6 Whitfield, P.J. et al. (2003) Invasion by schistosome cercariae: studies with human skin explants. Trends Parasitol. 19, 339–340 7 McKerrow, J.H. and Salter, J. (2002) Invasion of skin by Schistosoma cercariae. Trends Parasitol. 18, 193–195 8 Curwen, R.S. and Wilson, R.A. (2003) Invasion of skin by schistosome cercariae: some neglected facts. Trends Parasitol. 19, 63–66 9 McKerrow, J.H. (2003) Invasion of skin by schistosome cercariae: some neglected facts. Trends Parasitol. 19, 66–68 10 Ruppel, A. et al. (2004) Invasion by schistosome cercariae: neglected aspects in Schistosoma japonicum. Trends Parasitol. 20, 397–400 11 He, Y.X. (1990) The biology of Schistosoma. In Biology of Schistosome and Control of Schistosomiasis (Mao, S.P., ed.), p. 125, People’s Health Publishing House, Beijing 12 Haas, W. et al. (1987) Host identification by Schistosoma japonicum. J. Parasitol. 73, 568–577 13 Salafsky, B. et al. (1984) The role of essential fatty acids and prostagladin in cercarial penetration (Schistosoma mansoni). J. Parasitol. 70, 656–660 14 Hass, W. et al. (1994) Schistosoma haematobium cercarial host finding and host-recognition differs from that of S. mansoni. J. Parasitol. 80, 345–353 15 He, Y.X. et al. (1990) Penetration of Schistosoma japonicum cercariae into host skin. Chin. Med. J (Engl) 103, 34–44 16 He, Y.X. and Xie, M. (1994) Ultrastructural observations on cercaria of Schistosoma japonicum. Southeast Asian J. Trop. Med. Public Health 25, 501–508 17 He, Y.X. (1993) Biology of Schistosoma japonicum: from cercaria penetrating into host skin to producing eggs. Chin. Med. J (Engl) 106, 576–583 18 He, Y.X. et al. (1985) Histochemical and scanning electronmicroscopical observations on cercariae of Schistosoma japonicum. Acta Zool. Sin. 31, 6–11 19 Salter, J.P. et al. (2002) Cercarial elastase is encoded by a functionally conserved gene family across multiple species of schistosomes. J. Biol. Chem. 277, 24618–24624 20 He, Y.X. and Yang, H.Z. (1980) Physiological studies on the postcercarial development of Schistosoma japonicum. Acta Zool. Sin 26, 32–39 21 Burden, C.S. and Ubelaker, J.E. (1981) Schistosoma mansoni and Schistosoma haematobium: difference in development. Exp. Parasitol. 51, 28–34 22 Smith, M. et al. (1976) Culture of Schistosoma haematobium in vivo and in vitro. Ann. Trop. Med. Parasitol. 70, 101–107 23 Lozzi, S.P. et al. (1996) Involvement of regional lymph nodes after penetration of Schistosoma mansoni cercariae in naive and infected mice. Mem. Inst. Oswaldo Cruz 91, 491–498 24 Bayssade-Dufour, C. et al. (1994) Speed of skin penetration and initial migration route of infective larvae of Schistosoma haematobium in Meriones unguiculatus. C. R. Acad. Sci. III 317, 529–533 25 Gui, M. et al. (1995) Schistosoma japonicum and S. mansoni: comparison of larval migration patterns in mice. J. Helminthol. 69, 19–25 26 He, Y.X. et al. (1988) Death of newly transformed schistosomula during penetration of Schistosoma japonicum cercariae into different host skin. Acta Zool. Sin 34, 265–270 27 Clegg, J.A. and Smithers, S.R. (1968) Death of schistosome cercariae during penetration of the skin. II. Penetration of mammalian skin by Schistosoma mansoni. Parasitology 58, 111–128 28 Ghandour, A.M. and Webbe, G. (1976) A comparative study of the death of Schistosomula of Schistosoma haematobium and Schistosoma mansoni in the skin of mice and hamster. J. Helminthol. 50, 39–43 29 He, Y.X. et al. (2001) Host–parasite relationships of Schistosoma japonicum in mammalian hosts. Trends Parasitol. 17, 320–324 1471-4922/$ - see front matter Q 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.pt.2005.03.003
TRENDS in Parasitology
Vol.21 No.5 May 2005
Research Focus
Comparison of skin invasion among three major species of Schistosoma Yi-Xun He, Bernard Salafsky and Kalyanasundaram Ramaswamy Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL 61107, USA
A comparison of the host-finding behavior, mode of skin invasion and skin-migratory patterns of the three major schistosomes of humans reveals major differences. Among the three species, Schistosoma japonicum is remarkable at conserving energy during the host-finding process, and exhibiting swift migration through the skin to reach the predilection site sooner and mature earlier compared with Schistosoma mansoni and Schistosoma haematobium. In this article, we summarize and compare the penetration and migratory behavior of schistosomula of the three major human schistosomes through mouse and human skin. Skin-penetration behavior Human schistosomiasis infections occur when cercariae penetrate intact skin. Current knowledge of the skinpenetration behavior of schistosome cercariae is based mainly on studies using mouse models, and O90% of these studies used Schistosoma mansoni as the model [1–4]. The findings from these studies have been generalized to other species of schistosome. Unfortunately, the migratory behavior of cercariae through human skin has not been studied extensively [5,6]. Several recent publications in Trends in Parasitology [6–10] have dealt with the skinpenetration behavior of S. mansoni, but there is still a large gap in the understanding of the host–parasite relationships of Schistosoma japonicum and Schistosoma haematobium in the skin. Disparate but important data regarding S. japonicum and S. haematobium have been published in non-English peer-reviewed journals [11]. Host finding Cercariae of the three major schistosome species show marked differences in their migratory behavior through water before entering mammalian skin. Cercariae of S. japonicum swim to the top layer of water and rest there by floating with their ventral sides up and their tails bent down dorsally [11]. This behavior maximizes their chance of finding the host, while expending minimum energy and potentially prolonging their lives. Cercariae of S. mansoni and S. haematobium, however, are distributed throughout the body of water and rest only transiently, with their tails pointed towards the water surface and their bodies oriented down. Host finding by schistosome cercariae is a complex multistep procedure in which cercariae respond to Corresponding author: Ramaswamy, K. ([email protected]). Available online 18 March 2005 www.sciencedirect.com
thermostatic gradients or chemical cues from the host that eventually orient them to host skin [12]. Cercariae of S. haematobium are more sensitive to thermal gradients than to chemical cues, whereas S. mansoni relies largely on chemical signals to identify the host [13,14]. However, chemical cues seem to have no major role in the hostfinding behavior of S. japonicum cercariae [12]. Cercariae of S. japonicum can attach passively to the skin while the host pulls the body out of the water, thus enabling the cercariae to expend minimum energy in this process (Y-X. He, unpublished). Following this, thermal gradient seems to have a role in their creeping action onto the skin [4,12]. Thus, the three major schistosomes differ slightly in their host-finding behavior.
Cercarial penetration of host skin After the host is identified, the cercariae attach to the epidermis using their ventral suckers. The anterior part of schistosome cercariae has a specialized head organ that can stretch out and retract slightly [15] (Figure 1a). This head organ is used initially to find a suitable place for invasion [4]. The apex of the head organ forms a slightly elevated disc-like area at which the external opening of the acetabular gland ducts is present [16]. The secretions from these glands are sticky and are released into the microenvironment in large quantities after stimulation [11] (Figure 1b). They are rich in elastase enzymes (cercarial proteases) that assist skin penetration [17–19]. Substantial information is available regarding the nature and function of the cercarial enzymes in S. mansoni [9]. However, only limited information is available about the cercarial enzymes of S. japonicum, especially considering that S. japonicum cercariae differ in their host spectrum and migratory behavior. It has been shown that both gelatin and starch-agar film substrates are lysed by cercariae of S. japonicum following incubation at 378C for 7 h [15,17] (Figure 1c). This suggests that both protease and polysaccharase enzyme activities are present in the secretions from S. japonicum cercariae. The mechanical movement of the head organ, and the protease enzymes secreted from the head and acetabular glands help the initial forced entry of the parasite into the skin [9,15,18,19]. Secretions from the head gland are also important for subsequent migration of the parasite through the basement membrane and blood-vessel wall [8]. Typically, cercariae and schistosomula enter the stratum corneum of the skin at a 408 angle [4,15], not vertically as had been reported previously [1]. Similarly,
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Figure 1. (a) Scanning electron micrograph of the head organ of a Schistosoma japonicum cercaria. Scale barZ2 mm. Image reproduced, with permission, from Ref. [15]. (b) Three cercariae of S. japonicum are seen discharging copious amounts of their head and/or acetabular gland contents. Image reproduced, with permission, from Ref. [11]. (c) A living cercaria of S. japonicum was incubated in gelatin film at 378C for 7 h. Note the prominent area of gelatin lysed around the anterior end of the cercaria. Image reproduced, with permission, from Ref. [15]. Scale bars in (b,c)Z100 mm.
cercariae of all three major schistosomes can penetrate and enter mouse or human skin through any skin surface, irrespective of hair follicles or sebaceous glands [4,5,15]. Skin-migratory patterns Although entry of cercariae into host skin occurs within minutes, there seem to be major differences in the skinmigratory behavior of the three major schistosomes. During the initial 2 h after exposure, O50% of S. japonicum schistosomula were present in the dermis of both human and mouse. By 24 h, however, nearly 100% of the parasites had left the mouse epidermis [4]. The migratory pattern of S. japonicum through human skin is similar to that through mouse skin except for a slight delay in migration through human epidermis. Nevertheless, schistosomula of S. japonicum were seen inside the dermal blood vessels of humans as early as 2 h after exposure to infection [5] (Figure 2a) and inside the hypodermal vessels of mice within 24 h after infection [15] (Figure 2b). Entry of the schistosomula into blood vessels also seems to occur in an oblique fashion, virtually ripping through the vessel wall. Faster migration of S. japonicum through host tissue potentially enables it to reach the predilection site sooner than S. mansoni and S. haematobium, and to mature early. It has been reported that S. japonicum oviposition occurs within 24–27 days [20],
(a)
(b)
whereas it takes 30–35 days and 60–63 days for S. mansoni and S. haematobium, respectively [21]. Migratory patterns of S. mansoni through host skin seem to be different from those of S. japonicum. Eight hours after exposure to infection, 94% of the schistosomula of S. mansoni were present in the epidermis of human skin [5], whereas only 59% were present in mouse skin epidermis. When examined 24 h after infection, nearly 89% of the S. mansoni schistosomula were still in the epidermis of human skin [5]. In fact, live schistosomula were present in human skin epidermis 96 h after infection. The average thickness of mouse abdominal skin epidermis is 0.037 mm (ranging from 0.021 mm to 0.046 mm), whereas the average thickness of human foreskin epidermis is 0.143 mm (ranging from 0.121 mm to 0.164 mm). Thus, the thickness of human epidermis is approximately four times that of mouse epidermis. This might explain the initial slower migration of S. mansoni schistosomula through human epidermis. Despite this slower migration, the majority of the schistosomula reaches the dermis within 48 h after infection in both mouse (68%) and human (60%) skin. Within 72 h after infection, 90% (mouse skin) and 71% (human skin) of schistosomula were present in the dermis, mostly close to blood vessels [5] (Figure 2c). The migratory pattern of S. haematobium schistosomula through human [5] and hamster [22] skin seems to
(c)
Figure 2. (a) Human skin 2 h after exposure to 150 cercariae of Schistosoma japonicum. Note the presence of a schistosomulum (arrowed) inside the dermal vessel. Image reproduced, with permission, from Ref. [5]. (b) Mouse skin 24 h after infection with 300 cercariae of S. japonicum. A schistosomulum is seen ripping through the vessel wall of a hypodermal blood vessel. Note that the parasite is entering the vessel at an angle. Image reproduced, with permission, from Ref. [15]. Scale bars in (a,b)Z100 mm. (c) Human skin 72 h after infection with 150 cercariae of Schistosoma mansoni. Note the presence of a schistosomulum (arrowed) close to the blood vessel. Scale barZ50 mm. Image reproduced, with permission, from Ref. [5]. www.sciencedirect.com
Update
TRENDS in Parasitology
be similar to that of S. mansoni. More than 93% of S. haematobium schistosomula were seen only in the epidermis 8 h after exposure of human skin to infection [5]. Approximately 48–72 h after infection, the majority of S. haematobium schistosomula was seen entering the dermis and, within 72 h, several of these schistosomula were seen close to the blood vessels. Similar findings were observed in hamster skin [22]. The presence of several schistosomula within the dermal or hypodermal blood vessels suggests that all three major human schistosomes can use blood as their major route of migration from the skin to the lungs. However, schistosomula of S. japonicum are also occasionally seen inside lymphatic vessels in human skin (Y-X. He, unpublished), as has been reported for S. mansoni in mice [23] and S. haematobium in gerbils [24]. Thus, schistosomula of S. mansoni and S. haematobium take nearly three days to complete their skin migration, whereas those of S. japonicum complete their migration in just one day [5,17], and peak numbers of S. japonicum schistosomula arrive in the lungs approximately three days after infection [25]. Not all cercariae that attempt to penetrate the skin make it: some die in the process [26–28]. Interestingly, the death of newly transformed schistosomula during skin penetration was substantially lower for S. japonicum (7%) [26] than for S. mansoni (28–43%) [27] or S. haematobium (30%) [28]. Thus, overall, S. japonicum has better survival strategies, which might explain its ability to establish itself in a wide spectrum of hosts [29]. Future perspectives A comparison of the host-finding, skin-penetration and migratory behaviors of the three major species of human schistosome reveals major differences. Migratory behavior of the schistosomula of S. japonicum in human and mouse skin is virtually the same. However, the other two species of schistosome seem to migrate more slowly, especially in human skin. The schistosomula of S. japonicum complete their skin migration in one day, whereas those of S. mansoni and S. haematobium take three to five days to do so. The factors that help the schistosomula of S. japonicum to migrate faster through the skin and to become established in the host sooner are unknown. As more data about the functional proteomics of these parasites become available, a complete picture of the molecular mechanism of skin penetration will emerge and will help to identify a potential target for drug or vaccine development against skin-penetrating or lung-stage parasites. Acknowledgements Financial support was provided by NIH grant AI39066.
References 1 Gordon, R.M. and Griffiths, R.B. (1951) Observations on the means by which the cercariae of Schistosoma mansoni penetrate mammalian skin, together with an account of certain morphological changes observed in the newly penetrated larvae. Ann. Trop. Med. Parasitol. 45, 227–243 2 Stirewalt, M.A. and Dorsey, C.H. (1974) Schistosoma mansoni: cercarial penetration of host epidermis at the ultrastructural level. Exp. Parasitol. 35, 1–15 www.sciencedirect.com
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