Reorganization of Extracellular Matrix in Placentas from Women with Asymptomatic Chagas Disease: Mechanism of Parasite Invasion or Local Placental Defense?
Chagas disease, produced by the protozoan Trypanosoma cruzi (T. cruzi), is one of the most frequent endemic diseases in Latin America. In spite the fact that in the past few years T. cruzi congenital transmission has become of epidemiological importance, studies about this mechanism of infection are scarce. In order to explore some morphological aspects of this infection in the placenta, we analyzed placentas from T. cruzi-infected mothers by immunohistochemical and histochemical methods. Infection in mothers, newborns, and placentas was confirmed by PCR and by immunofluorescence in the placenta. T. cruzi-infected placentas present destruction of the syncytiotrophoblast and villous stroma, selective disorganization of the basal lamina, and disorganization of collagen I in villous stroma. Our results suggest that the parasite induces reorganization of this tissue component and in this way may regulate both inflammatory and immune responses in the host. Changes in the ECM of placental tissues, together with the immunological status of mother and fetus, and parasite load may determine the probability of congenital transmission of T. cruzi. 1. Introduction American Trypanosomiasis, or Chagas disease, is a zoonosis caused by Trypanosoma cruzi (T. cruzi). Currently, 10 million people in the Americas, from Mexico in the north to Argentina and Chile in the south, are estimated to be infected [1]. For thousands of years, Chagas disease was known only in the Region of the Americas, mainly in Latin America, where it has been endemic [2]. In past decades, it has been increasingly detected in other non-endemic countries in the American (Canada and the United States), the Western Pacific (mainly Australia and Japan) and the European continents. The presence of Chagas disease outside Latin America is the result of population mobility, notably migration, but cases have been reported among travelers returning from Latin America and even in adopted children [3]. Subsequent transmission occurs through transfusion, vertical, and transplantation routes [3]. The vertical transmission of T. cruzi cannot be prevented, but early detection and treatment of congenital infection achieves cure rates close to 100 per cent [4]. Fetal and maternal tissues are separated by a fetal epithelium (the trophoblast), the greatest area of which is in the villous placenta, the site of nutrient and gas exchange [5]. The human placenta is classified as a hemochorial villous placenta in which the free chorionic villi are the functional units. These chorionic villi are formed by the trophoblast and
References
[1]
First WHO report on neglected tropical diseases: working to overcome the global impact of neglected tropical diseases, 2010.
[2]
A. Araújo, A. M. Jansen, K. Reinhard, and L. F. Ferreira, “Paleoparasitology of chagas disease—a review,” Memorias do Instituto Oswaldo Cruz, vol. 104, supplement 1, pp. 9–16, 2009.
[3]
G. A. Schmunis, “Epidemiology of Chagas disease in non-endemic countries: the role of international migration,” Memorias do Instituto Oswaldo Cruz, vol. 102, supplement 1, pp. 75–85, 2007.
[4]
Chagas disease control and prevention in Europe. Report of a WHO Informal Consultation (jointly organized by WHO headquarters and the WHO Regional Office for Europe), World Health Organization, Geneva, Switzerland, 2010.
[5]
K. Berniscke, P. Kaufmann, and R. N. Baergen, Pathology of the Human Placenta, Springer, New York, NY, USA, 2006.
[6]
J. Duaso, G. Rojo, G. Cabrera et al., “Trypanosoma cruzi induces tissue disorganization and destruction of chorionic villi in an ex vivo infection model of human placenta,” Placenta, vol. 31, no. 8, pp. 705–711, 2010.
[7]
U. Kemmerling, C. Bosco, and N. Galanti, “Infection and invasion mechanisms of Trypanosoma cruzi in the congenital transmission of chagas' disease: a proposal,” Biological Research, vol. 43, no. 3, pp. 307–316, 2010.
[8]
A. L. Bittencourt, “Congenital chagas disease,” American Journal of Diseases of Children, vol. 130, no. 1, pp. 97–103, 1976.
[9]
A. M. Altemani, A. L. Bittencourt, and A. M. A. Lana, “Immunohistochemical characterization of the inflammatory infiltrate in placental Chagas' disease: a qualitative and quantitative analysis,” American Journal of Tropical Medicine and Hygiene, vol. 62, no. 2, pp. 319–324, 2000.
[10]
I. Zulantay, P. Honores, A. Solari et al., “Use of polymerase chain reaction (PCR) and hybridization assays to detect Trypanosoma cruzi in chronic chagasic patients treated with itraconazole or allopurinol,” Diagnostic Microbiology and Infectious Disease, vol. 48, no. 4, pp. 253–257, 2004.
[11]
G. Cabrera, I. Espinoza, U. Kemmerling, and N. Galanti, “Mesocestoides corti: morphological features and glycogen mobilization during in vitro differentiation from larva to adult worm,” Parasitology, vol. 137, no. 3, pp. 373–384, 2010.
[12]
G. E. B. Marcon, P. D. Andrade, D. M. De Albuquerque et al., “Use of a nested polymerase chain reaction (N-PCR) to detect Trypanosoma cruzi in blood samples from chronic chagasic patients and patients with doubtful serologies,” Diagnostic Microbiology and Infectious Disease, vol. 43, no. 1, pp. 39–43, 2002.
[13]
M. Faúndez, R. López-Mu?oz, G. Torres et al., “Buthionine sulfoximine has anti-Trypanosoma cruzi activity in a murine model of acute Chagas' disease and enhances the efficacy of nifurtimox,” Antimicrobial Agents and Chemotherapy, vol. 52, no. 5, pp. 1837–1839, 2008.
[14]
J. R. Coura, “Chagas disease: what is known and what is needed—a background article,” Memorias do Instituto Oswaldo Cruz, vol. 102, no. 1, pp. 113–122, 2007.
[15]
M. F. Triquell, C. Díaz-Luján, H. Freilij, P. Paglini, and R. E. Fretes, “Placental infection by two subpopulations of Trypanosoma cruzi is conditioned by differential survival of the parasite in a deleterious placental medium and not by tissue reproduction,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 103, no. 10, pp. 1011–1018, 2009.
[16]
C. Frantz, K. M. Stewart, and V. M. Weaver, “The extracellular matrix at a glance,” Journal of Cell Science, vol. 123, no. 24, pp. 4195–4200, 2010.
[17]
H. J?rvel?inen, A. Sainio, M. Koulu, T. N. Wight, and R. Penttinen, “Extracellular matrix molecules: potential targets in pharmacotherapy,” Pharmacological Reviews, vol. 61, no. 2, pp. 198–223, 2009.
[18]
B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts, and P. Walter, Molecular Biology of the Cell, Garland Science, New York, NY, USA, 5th edition, 2008.
[19]
A. P. M. P. Marino, A. A. Silva, R. T. Pinho, and J. Lannes-Vieira, “Trypanosoma cruzi infection: a continuous invader-host cell cross talk with participation of extracellular matrix and adhesion and chemoattractant molecules,” Brazilian Journal of Medical and Biological Research, vol. 36, no. 8, pp. 1121–1133, 2003.
[20]
Y. Carlier, “Factors and mechanisms involved in the transmission and development of congenital infection with Trypanosoma cruzi,” Revista da Sociedade Brasileira de Medicina Tropical, vol. 38, pp. 105–107, 2005.
[21]
E. Hermann, C. Truyens, C. Alonso-Vega et al., “Human fetuses are able to mount an adultlike CD8 T-cell response,” Blood, vol. 100, no. 6, pp. 2153–2158, 2002.
[22]
E. Hermann, C. Alonso-Vega, A. Berthe et al., “Human congenital infection with Trypanosoma cruzi induces phenotypic and functional modifications of cord blood NK cells,” Pediatric Research, vol. 60, no. 1, pp. 38–43, 2006.
[23]
J. Vekemans, C. Truyens, F. Torrico et al., “Maternal Trypanosoma cruzi infection upregulates capacity of uninfected neonate cells to produce pro- and anti-inflammatory cytokines,” Infection and Immunity, vol. 68, no. 9, pp. 5430–5434, 2000.
[24]
Y. Carlier and C. Truyens, “Maternal-Fetal Transmission of Trypanosoma cruzi,” in American Trypanosomiasis Chagas Disease One Hundred years of Research, J. Telleria and M. Tibayrenc, Eds., pp. 539–581, Elsevier, New York, NY, USA, 2010.
[25]
E. Moretti, B. Basso, I. Castro et al., “Chagas' disease: study of congenital transmission in cases of acute maternal infection,” Revista da Sociedade Brasileira de Medicina Tropical, vol. 38, no. 1, pp. 53–55, 2005.
[26]
C. D. Luján, M. F. Triquell, A. Sembaj, C. E. Guerrero, and R. E. Fretes, “Trypanosoma cruzi: productive infection is not allowed by chorionic villous explant from normal human placenta in vitro,” Experimental Parasitology, vol. 108, no. 3-4, pp. 176–181, 2004.
[27]
W. P. Daley, S. B. Peters, and M. Larsen, “Extracellular matrix dynamics in development and regenerative medicine,” Journal of Cell Science, vol. 121, no. 3, pp. 255–264, 2008.
[28]
P. N. Nde, K. J. Simmons, Y. Y. Kleshchenko, S. Pratap, M. F. Lima, and F. Villalta, “Silencing of the larninin γ-1 gene blocks Trypanosoma cruzi infection,” Infection and Immunity, vol. 74, no. 3, pp. 1643–1648, 2006.
[29]
A. P. C. A. Lima, P. C. Almeida, I. L. S. Tersariol et al., “Heparan sulfate modulates kinin release by Trypanosoma cruzi through the activity of cruzipain,” The Journal of Biological Chemistry, vol. 277, no. 8, pp. 5875–5881, 2002.
[30]
J. Scharfstein and A. Morrot, “A role for extracellular amastigotes in the immunopathology of chagas disease,” Memorias do Instituto Oswaldo Cruz, vol. 94, supplement 1, pp. 51–63, 1999.
[31]
F. R. S. Gutierrez, M. M. Lalu, F. S. Mariano et al., “Increased activities of cardiac matrix metalloproteinases matrix metalloproteinase (MMP)-2 and MMP-9 are associated with mortality during the acute phase of experimental Trypanosoma cruzi infection,” Journal of Infectious Diseases, vol. 197, no. 10, pp. 1468–1476, 2008.
[32]
C. M. Calvet, F. O. R. Oliveira, T. C. Araújo-Jorge, and M. C. S. Pereira, “Regulation of extracellular matrix expression and distribution in Trypanosoma cruzi-infected cardiomyocytes,” International Journal of Medical Microbiology, vol. 299, no. 4, pp. 301–312, 2009.