Acute schistosomiasis is associated with a primary exposure and is more commonly seen in nonimmune individuals traveling through endemic regions. In this study, we have focused on the cytokine profile of T lymphocytes evaluated in circulating leukocytes of acute Schistosomiasis mansoni-infected patients (ACT group) before and after praziquantel treatment (ACT-TR group). Our data demonstrated increased values of total leukocytes, eosinophils, and monocytes in both groups. Interestingly, we have observed that patients treated with praziquantel showed increased values of lymphocytes as compared with noninfected group (NI) or ACT groups. Furthermore, a decrease of neutrophils in ACT-TR was observed when compared to ACT group. Analyses of short-term in vitro whole blood stimulation demonstrated that, regardless of the presence of soluble Schistosoma mansoni eggs antigen (SEA), increased synthesis of IFN-γ and IL-4 by T-cells was observed in the ACT group. Analyses of cytokine profile in CD8 T cells demonstrated higher percentage of IFN-γ and IL-4 cells in both ACT and ACT-TR groups apart from increased percentage of IL-10 cells only in the ACT group. This study is the first one to point out the relevance of CD8 T lymphocytes in the immune response induced during the acute phase of schistosomiasis. 1. Introduction Schistosomiasis is a tropical parasitic chronic disease, caused by worms of the genus Schistosoma. The infection is endemic in tropics and subtropics around the world and is present in Africa, South America, Arabia, and Asia. There are approximately 200 million people infected worldwide, and the number of deaths caused by schistosomiasis is estimated at around 41.000 annually [1]. Schistosoma mansoni worms dwell in peri-intestinal venules and cause intestinal, hepatointestinal, and hepatosplenic schistosomiasis [2]. Brazil is the country most affected by schistosomiasis in the Americas, with 1.5 million people infected and more than 36 million at risk of acquiring infection [3, 4]. In the state of Minas Gerais, Schistosomiasis mansoni is prevalent in 519 municipalities, with an estimated number of one million people infected [5]. The propagation and maintenance of schistosomiasis in a given region are conditional of many factors such as appropriate climate, socioeconomic conditions, rapid spread of intermediate hosts, sanitary conditions, and water supply [6]. Tourist activity in endemic areas may be an important contributing factor to the propagation of outbreaks/cases of schistosomiasis [7–10]. In endemic areas for schistosomiasis, people develop
References
[1]
WHO, World Health Organization, Geneva, Switzerland, 2012, http://whqlibdoc.who.int/publications/2010/9789241564090_eng.pdf.
[2]
B. Gryseels, “Schistosomiasis,” International Journal of Infectious Diseases, vol. 26, pp. 383–397, 2012.
[3]
P. Steinmann, J. Keiser, R. Bos, M. Tanner, and J. Utzinger, “Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk,” Lancet Infectious Diseases, vol. 6, no. 7, pp. 411–425, 2006.
[4]
J. R. Lambertucci, “Acute schistosomiasis mansoni: revisited and reconsidered,” Memorias Do Instituto Oswaldo Cruz, vol. 105, no. 4, pp. 422–435, 2010.
[5]
N. Katz, “Schistosomiasis control in Brazil,” Memorias Do Instituto Oswaldo Cruz, vol. 93, pp. 33–35, 1998.
[6]
R. S. Do Amaral, P. L. Tauil, D. D. Lima, and D. Engels, “An analysis of the impact of the Schistosomiasis Control Programme in Brazil,” Memorias Do Instituto Oswaldo Cruz, vol. 101, no. 1, pp. 79–85, 2006.
[7]
C. S. Barbosa, S. M. L. Montenegro, F. G. C. Abath, and A. L. Coutinho Domingues, “Specific situations related to acute schistosomiasis in Pernambuco, Brazil,” Memorias Do Instituto Oswaldo Cruz, vol. 96, pp. 169–172, 2001.
[8]
C. S. Barbosa, A. L. Domingues, F. Abath et al., “An outbreak of acute schistosomiasis at Porto de Galinhas beach, Pernambuco, Brazil,” Cadernos De Saude Publica, vol. 17, no. 3, pp. 725–728, 2001.
[9]
A. R. De Jesus, A. Silva, L. B. Santana et al., “Clinical and immunologic evaluation of 31 patients with acute schistosomiasis mansoni,” Journal of Infectious Diseases, vol. 185, no. 1, pp. 98–105, 2002.
[10]
M. J. Enk, R. L. Caldeira, O. S. Carvalho, and V. T. Schall, “Rural tourism as risk factor for the transmission of schistosomiasis in Minas Gerais, Brazil,” Memorias Do Instituto Oswaldo Cruz, vol. 99, no. 5, pp. 105–108, 2004.
[11]
R. Veronsi and R. Focaccia, Tratado De Infectologia, Atheneu, Rio de Janeiro, Brazil, 2 edition, 2002.
[12]
L. Q. Nguyen, J. Estrella, E. A. Jett, E. L. Grunvald, L. Nicholson, and D. L. Levin, “Acute schistosomiasis in nonimmune travelers: Chest CT findings in 10 patients,” American Journal of Roentgenology, vol. 186, no. 5, pp. 1300–1303, 2006.
[13]
R. Corrêa-Oliveira, L. C. C. Malaquias, P. L. Falc？o et al., “Cytokines as determinants of resistance and pathology in human Schistosoma mansoni infection,” Brazilian Journal of Medical and Biological Research, vol. 31, no. 1, pp. 171–177, 1998.
[14]
S. A. Rezende, J. R. Lambertucci, and A. M. Goes, “Role of immune complexes from pacients with different clinical forms of schistosomiasis in the modulation of in vitro granuloma reaction,” Memorias Do Instituto Oswaldo Cruz, vol. 92, no. 5, pp. 683–687, 1997.
[15]
X. Liu, T. Kohyama, H. Wang et al., “Th2 cytokine regulation of type I collagen gel contraction mediated by human lung mesenchymal cells,” American Journal of Physiology, vol. 282, no. 5, pp. L1049–L1056, 2002.
[16]
R. M. Reiman, R. W. Thompson, C. G. Feng et al., “Interleukin-5 (IL-5) augments the progression of liver fibrosis by regulating IL-13 activity,” Infection and Immunity, vol. 74, no. 3, pp. 1471–1479, 2006.
[17]
T. R. Mosmann and K. W. Moore, “The role of IL-10 in crossregulation of TH1 and TH2 responses,” Immunology Today, vol. 12, no. 3, pp. A49–A53, 1991.
[18]
M. Booth, J. K. Mwatha, S. Joseph et al., “Periportal fibrosis in human Schistosoma mansoni infection is associated with low IL-10, Low IFN-γ, high TNF-α, or low RANTES, depending on age and gender,” Journal of Immunology, vol. 172, no. 2, pp. 1295–1303, 2004.
[19]
S. M. L. Montenegro, P. Miranda, S. Mahanty et al., “Cytokine production in acute versus chronic human schistosomiasis mansoni: the cross-regulatory role of interferon-γ and interleukin-10 in the responses of peripheral blood mononuclear cells and splenocytes to parasite antigens,” Journal of Infectious Diseases, vol. 179, no. 6, pp. 1502–1514, 1999.
[20]
N. Katz, A. Chaves, and J. Pellegrino, “A simple device for quantitative stool thick-smear technique in schistosomiasis mansoni,” Revista Do Instituto de Medicina Tropical de Sao Paulo, vol. 14, no. 6, pp. 397–400, 1972.
[21]
J. G. Hardman, L. E. Limbird, and A. G. Gilman, Eds., Goodman & Gilman’s. The Pharmacological Basis of Therapeutics, vol. 2045, McGraw-Hill, New York, NY, USA, 10th edition, 2001.
[22]
M. F. Abdel-Wahab, G. Esmat, A. Farrag, Y. A. El-Boraey, and G. T. Strickland, “Grading of hepatic schistosomiasis by the use of ultrasonography,” American Journal of Tropical Medicine and Hygiene, vol. 46, no. 4, pp. 403–408, 1992.
[23]
M. Homeida, A. F. Abdel-Gadir, A. W. Cheever et al., “Diagnosis of pathologically confirmed Symmers' periportal fibrosis by ultrasonography: a prospective blinded study,” American Journal of Tropical Medicine and Hygiene, vol. 38, no. 1, pp. 86–91, 1988.
[24]
G. G. Cerri, V. A. Alves, and A. Magalhaes, “Hepatosplenic schistosomiasis mansoni: ultrasound manifestations,” Radiology, vol. 153, no. 3, pp. 777–780, 1984.
[25]
G. Gazzinelli, N. Katz, R. S. Rocha, and D. G. Colley, “Immune responses during human schistosomiasis mansoni. X. Production and standardization of an antigen-induced mitogenic activity by peripheral blood mononuclear cells from treated, but not active cases of schistosomiasis,” Journal of Immunology, vol. 130, no. 6, pp. 2891–2895, 1983.
[26]
D. Silveira-Lemos, A. Teixeira-Carvalho, A. O. Martins-Filho et al., “Eosinophil activation status, cytokines and liver fibrosis in Schistosoma mansoni infected patients,” Acta Tropica, vol. 108, no. 2-3, pp. 150–159, 2008.
[27]
M. N. Lunde and E. A. Ottesen, “Enzyme-linked immunosorbent assay (ELISA) for detecting IgM and IgE antibodies in human schistosomiasis,” American Journal of Tropical Medicine and Hygiene, vol. 29, no. 1, pp. 82–85, 1980.
[28]
B. Evengard, L. Hammarstrom, C. I. E. Smith, and E. Linder, “Early antibody responses in human schistosomiasis,” Clinical and Experimental Immunology, vol. 80, no. 1, pp. 69–76, 1990.
[29]
A. Rabello, “Acute human schistosomiasis mansoni,” Memórias Do Instituto Oswaldo Cruz, vol. 90, no. 2, pp. 277–280, 1995.
[30]
S. B. Pessoa and J. P. Amorim, “Notas sobre a esquistossomose mans？nica em algumas localidades de Alagoas,” Revista Brasileira De Medicina, vol. 14, pp. 420–422, 1957.
[31]
K. Kloetzel, “Schistosomiasis in Brazil: does social development suffice?” Parasitology Today, vol. 5, no. 12, pp. 388–391, 1989.
[32]
M. F. Costa-Silva, Acompanhamento clínico, epidemiológico e imunológico de pacientes portadores da fase aguda da esquistossomose mansoni, submetidos à terapêutica específica com Praziquantel [Disserta？？o (Mestrado em Doen？as Infecciosas e Parasitárias)], Funda？？o Oswaldo Cruz. Centro de Pesquisas René Rachou. Programa de Pós-gradua？？o em Ciências da Saúde, Belo Horizonte, Brazil, 2009, http://www.cpqrr.fiocruz.br/texto-completo/D_5.pdf.
[33]
J. R. Coura and R. S. Amaral, “Epidemiological and control aspects of schistosomiasis in Brazilian endemic areas,” Memorias Do Instituto Oswaldo Cruz, vol. 99, no. 5, pp. 13–19, 2004.
[34]
C. H. Barata, R. A. Pinto-Silva, and J. R. Lambertucci, “Abdominal ultrasound in acute schistosomiasis mansoni,” British Journal of Radiology, vol. 72, pp. 949–952, 1999.
[35]
G. J. Race, R. M. Michaels, J. H. Martin, J. E. Larsh Jr., and J. L. Matthews, “Schistosoma mansoni eggs: an electron microscopic study of shell pores and microbarbs,” Proceedings of the Society for Experimental Biology and Medicine, vol. 130, no. 3, pp. 990–992, 1969.
[36]
A. Sher, R. L. Coffman, S. Hieny, P. Scott, and A. W. Cheever, “Interleukin 5 is required for the blood and tissue eosinophilia but not granuloma formation induced by infection with Schistosoma mansoni,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 1, pp. 61–65, 1990.
[37]
H. L. Lenzi, R. G. Pacheco, M. Pelajo-Machado, M. S. Panasco, W. S. Romanha, and J. A. Lenzi, “Immunological system and Schistosoma mansoni: co-evolutionary immunobiology. what is the eosinophil role in parasite-host relationship?” Memorias Do Instituto Oswaldo Cruz, vol. 92, pp. 19–32, 1997.
[38]
S. R. Smithers, D. J. McLaren, and F. J. Ramalho-Pinto, “Immunity to schistosomes: the target,” The American Journal of Tropical Medicine and Hygiene, vol. 26, no. 6, pp. 11–19, 1977.
[39]
E. Caumes and M. Vidailhet, “Acute neuroschistosomiasis: a cerebral vasculitis to treat with corticosteroids not praziquantel,” Journal of Travel Medicine, vol. 17, no. 5, pp. 359–361, 2010.
[40]
D. C. Cara, D. Negrao-Correa, and M. M. Teixeira, “Mechanisms underlying eosinophil trafficking and their relevance in vivo,” Histology and Histopathology, vol. 15, no. 3, pp. 899–920, 2000.
[41]
R. Borojevic, C. G. Pinto, M. C. el-Cheikh, and H. S. Dutra, “Experimental murine schistosomiasis mansoni: hyperplasia of the mono-macrophage cell lineage and stimulation of myeloid proliferation by peripheral macrophages,” Brazilian Journal of Medical and Biological Research, vol. 22, no. 5, pp. 579–586, 1989.
[42]
I. M. el-Sharkawy, A. A. Ibrahim, and M. A. el-Bassuoni, “Neutrophil apoptosis in acute and chronic Schistosoma mansoni infection,” Journal of the Egyptian Society of Parasitology, vol. 32, no. 2, pp. 507–516, 2002.
[43]
T. R. Mosmann, L. Li, H. Hengartner, D. Kagi, W. Fu, and S. Sad, “Differentiation and functions of T cell subsets,” CIBA Foundation Symposia, vol. 204, pp. 148–158, 1997.
[44]
T. R. Mosmann and S. Sad, “The expanding universe of T-cell subsets: Th1, Th2 and more,” Immunology Today, vol. 17, no. 3, pp. 138–146, 1996.
[45]
L. R. Brunet, F. D. Finkelman, A. W. Cheever, M. A. Kopf, and E. J. Pearce, “IL-4 protects against TNF-α-mediated cachexia and death during acute schistosomiasis,” Journal of Immunology, vol. 159, no. 2, pp. 777–785, 1997.
[46]
P. G. Fallon, E. J. Richardson, P. Smith, and D. W. Dunne, “Elevated type 1, diminished type 2 cytokines and impaired antibody response are associated with hepatotoxicity and mortalities during Schistosoma mansoni infection of CD4-depleted mice,” European Journal of Immunology, vol. 30, no. 2, pp. 470–480, 2000.
[47]
P. Raso, “Esquistossomose mans？nica,” in Patologia, L. Bogliolo, Ed., pp. 534–545, Guanabara Koogan, Rio de Janeiro, Brazil, 4th edition, 1994.
[48]
P. J. Perrin and S. M. Phillips, “The molecular basis of granuloma formation in schistosomiasis. I. A T cell-derived suppressor effector factor,” Journal of Immunology, vol. 141, no. 5, pp. 1714–1719, 1988.
[49]
V. Pancré, M. Delacre, J. Herno, and C. Auriault, “Schistosomal egg antigen-responsive CD8 T-cell population in Schistosoma mansoni-infected BALB/c mice,” Immunology, vol. 98, no. 4, pp. 525–534, 1999.
[50]
R. Oliveira-Prado, I. R. Caldas, A. Teixeira-Carvalho, et al., “CD4+ and CD8+ distribution profile in individuals infected by Schistosoma mansoni,” Scandinavian Journal of Immunology, vol. 69, no. 6, pp. 521–528, 2009.
[51]
O. A. Martins-Filho, J. R. Mello, and R. Correa-Oliveira, “The spleen is an important site of T cell activation during human hepatosplenic schistosomiasis,” Memorias Do Instituto Oswaldo Cruz, vol. 93, supplement 1, pp. 159–164, 1998.
[52]
O. A. Martins-Filho, J. R. Cunha-Melo, J. R. Lambertucci, et al., “Clinical forms of human Schistosoma mansoni infection are associated with differential activation of T-cell subsets and costimulatory molecules,” Digestive Diseases and Sciences, vol. 44, no. 3, pp. 570–577, 1999.
[53]
A. Teixeira-Carvalho, O. A. Martins-Filho, Z. A. Andrade, J. R. Cunha-Mello, R. A. Wilson, and R. Corrêa-Oliveira, “The study of T-cell activation in peripheral blood and spleen of hepatosplenic patients suggests an exchange of cells between these two compartments in advanced human schistosomiasis mansoni infection,” Scandinavian Journal of Immunology, vol. 56, no. 3, pp. 315–322, 2002.
[54]
A. Teixeira-Carvalho, O. A. Martins-Filho, V. Peruhype-Magalh？es, et al., “Cytokines, chemokine receptors, T-cells and clinical forms of human schistosomiasis,” Acta Tropica, vol. 108, no. 2-3, pp. 139–149, 2008.
[55]
J. M. M. Den Haan and M. J. Bevan, “Antigen presentation to CD8+ T cells: cross-priming in infectious diseases,” Current Opinion in Immunology, vol. 13, no. 4, pp. 437–441, 2001.
[56]
B. J. Manfras, S. Reuter, T. Wendland, and P. Kern, “Increased activation and oligoclonality of peripheral CD8+T cells in the chronic human helminth infection alveolar echinococcosis,” Infection and Immunity, vol. 70, no. 3, pp. 1168–1174, 2002.
[57]
A. Kalinkovich, Z. Weisman, Z. Greenberg, et al., “Decreased CD4 and increased CD8 counts with T cell activation is associated with chronic helminth infection,” Clinical and Experimental Immunology, vol. 114, no. 3, pp. 414–421, 1998.
[58]
G. Borkow, Q. Leng, Z. Weisman, et al., “Chronic immune activation associated with intestinal helminth infections results in impaired signal transduction and anergy,” Journal of Clinical Investigation, vol. 106, no. 8, pp. 1053–1060, 2000.
[59]
E. P. Grant and K. L. Rock, “MHC class I-restricted presentation of exogenous antigen by thymic antigen-presenting cells in vitro and in vivo,” Journal of Immunology, vol. 148, no. 1, pp. 13–18, 1992.
[60]
K. L. Rock, S. Gamble, L. Rothstein, C. Gramm, and B. Benacerraf, “Dissociation of β2-microglobulin leads to the accumulation of a substantial pool of inactive class I MHC heavy chains on the cell surface,” Cell, vol. 65, no. 4, pp. 611–620, 1991.
[61]
K. L. Rock, C. Fleischacker, and S. Gamble, “Peptide-priming of cytolytic T cell immunity in vivo using β2- microglobulin as an adjuvant,” Journal of Immunology, vol. 150, no. 4, pp. 1244–1252, 1993.
[62]
M. Larsson, J. F. Fonteneau, and N. Bhardwaj, “Dendritic cells resurrect antigens fromdead cells,” Trends in Immunology, vol. 22, no. 3, pp. 141–148, 2001.
[63]
P. L. Falc？o, L. C. Malaquias, O. A. Martins-Filho, et al., “Human schistosomiasis mansoni: IL-10 modulates the in vitro granuloma formation,” Parasite Immunology, vol. 20, no. 10, pp. 447–454, 1998.
[64]
J. A. Pedras-Vasconcelos and E. J. Pearce, “Type 1 CD8+ T Cell responses during infection with the helminth Schistosoma mansoni,” Journal of Immunology, vol. 157, no. 7, pp. 3046–3053, 1996.
[65]
E. Doehring-Schwerdtfeger, I. M. Abdel-Rahim, R. Kardorff, et al., “Ultrasonographical investigation of periportal fibrosis in children with Schistosoma mansoni infection: reversibility of morbidity twenty-three months after treatment with praziquantel,” American Journal of Tropical Medicine and Hygiene, vol. 46, no. 4, pp. 409–415, 1992.
[66]
G. F. Cota, R. A. Pinto-Silva, C. M. Antunes, and J. R. Lambertucci, “Ultrasound and clinical investigation of hepatosplenic schistosomiasis: evaluation of splenomegaly and liver fibrosis four years after mass chemotherapy with oxamniquine,” American Journal of Tropical Medicine and Hygiene, vol. 74, no. 1, pp. 103–107, 2006.
[67]
Z. A. Andrade, A. P. Baptista, and T. S. Santana, “Remodeling of hepatic vascular changes after specific chemotherapy of schistosomal periportal fibrosis,” Memorias Do Instituto Oswaldo Cruz, vol. 101, no. 1, pp. 267–272, 2006.
[68]
J. H. Kihara, N. Muhoho, D. Njomo, et al., “Drug efficacy of praziquantel and albendazole in school children in mwea division, central province, kenya,” Acta Tropica, vol. 102, no. 3, pp. 165–171, 2007.
[69]
P. Martins-Leite, G. Gazzinelli, L. F. Alves-Oliveira, et al., “Effect of chemotherapy with praziquantel on the production of cytokines and morbidity associated with schistosomiasis mansoni,” Antimicrobial Agents and Chemotherapy, vol. 52, no. 8, pp. 2780–2786, 2008.
[70]
C. M. Fitzsimmons, S. Joseph, F. M. Jones, et al., “Chemotherapy for schistosomiasis in ugandan fishermen: treatment can cause a rapid increase in interleukin-5 levels in plasma but decreased levels of eosinophilia and worm-specific immunoglobulin E,” Infection and Immunity, vol. 72, no. 7, pp. 4023–4030, 2004.
[71]
S. Joseph, F. M. Jones, K. Walter, et al., “Increases in human T helper 2 cytokine responses to Schistosoma mansoni worm and worm-tegument antigens are induced by treatment with praziquantel,” Journal of Infectious Diseases, vol. 190, no. 4, pp. 835–842, 2004.
[72]
J. R. De Souza, C. N. Morais, M. L. Aroucha, et al., “Treatment of human acute schistosomiasis with oxamniquine induces an increase in interferon-γ response to Schistosoma mansoni antigens,” Memorias Do Instituto Oswaldo Cruz, vol. 102, no. 2, pp. 225–228, 2007.
[73]
R. Corrêa-Oliveira, I. Rodrigues Caldas, O. A. Martins-Filho, et al., “Analysis of the effects of treatment of human Schistosoma mansoni infection on the immune response of patients from endemic areas,” Acta Tropica, vol. 77, no. 1, pp. 141–146, 2000.
[74]
M. I. Araújo, A. R. De Jesus, O. Bacellar, E. Sabin, E. Pearce, and E. M. Carvalho, “Evidence of a T helper type 2 activation in human schistosomiasis,” European Journal of Immunology, vol. 26, no. 6, pp. 1399–1403, 1996.
[75]
J. L. Grogan, P. G. Kremsner, A. M. Deelder, and M. Yazdanbakhsh, “Elevated proliferation and interleukin-4 release from CD4+cells after chemotherapy in human schistosoma haematobium infection,” European Journal of Immunology, vol. 26, no. 6, pp. 1365–1370, 1996.
[76]
C. F. Brito, I. R. Caldas, P. Coura Filho, R. Corrêa-Oliveira, and S. C. Oliveira, “CD4+T cells of schistosomiasis naturally resistant individuals living in an endemic area produce interferon-γ and tumour necrosis factor-α in response to the recombinant 14KDA Schistosoma mansoni fatty acid-binding protein,” Scandinavian Journal of Immunology, vol. 51, no. 6, pp. 595–601, 2000.
