• 1.

    Chagas C, 1909. Nova tripanozomiase humana: estudos sobre a morfolojia e o ciclo evolutivo do Schizotrypanum cruzi n. gen., n. sp., ajente etiolojico de nova entidade morbida do homem. Mem Inst Oswaldo Cruz 1: 159218.

    • Search Google Scholar
    • Export Citation
  • 2.

    Moncayo A, 2003. Chagas disease: current epidemiological trends after the interruption of vectorial and transfusional transmission in the Southern Cone countries. Mem Inst Oswaldo Cruz 98: 577591.

    • Search Google Scholar
    • Export Citation
  • 3.

    Tanowitz HB, Weiss LM, Montgomery SP, 2011. Chagas disease has now gone global. PLoS Negl Trop Dis 5: e1136.

  • 4.

    Sánchez LV, Ramirez JD, 2013. Congenital and oral transmission of American trypanosomiasis: an overview of physiopathogenic aspects. Parasitology 140: 147159.

    • Search Google Scholar
    • Export Citation
  • 5.

    Prata A, 2001. Clinical and epidemiological aspects of Chagas disease. Lancet Infect Dis 1: 92100.

  • 6.

    Machado FS, Dutra WO, Esper L, Gollob KJ, Teixeira MM, Factor SM, Weiss LM, Nagajyothi F, Tanowitz HB, Garg NJ, 2012. Current understanding of immunity to Trypanosoma cruzi infection and pathogenesis of Chagas disease. Semin Immunopathol 34: 753770.

    • Search Google Scholar
    • Export Citation
  • 7.

    Ramírez G, Valck C, Aguilar L, Kemmerling U, López-Muñoz R, Cabrera G, Morello A, Ferreira J, Maya JD, Galanti N, Ferreira A, 2012. Roles of Trypanosoma cruzi calreticulin in parasite-host interactions and in tumor growth. Mol Immunol 52: 133140.

    • Search Google Scholar
    • Export Citation
  • 8.

    Valck C, Ramírez G, López N, Ribeiro CH, Maldonado I, Sánchez G, Ferreira VP, Schwaeble W, Ferreira A, 2010. Molecular mechanisms involved in the inactivation of the first component of human complement by Trypanosoma cruzi calreticulin. Mol Immunol 47: 15161521.

    • Search Google Scholar
    • Export Citation
  • 9.

    Ferreira V, Valck C, Sanchez G, Gingras A, Tzima S, Molina MC, Sim R, Schwaeble W, Ferreira A, 2004. The classical activation pathway of the human complement system is specifically inhibited by calreticulin from Trypanosoma cruzi. J Immunol 172: 30423050.

    • Search Google Scholar
    • Export Citation
  • 10.

    Ferreira V, Molina MC, Schwaeble W, Lemus D, Ferreira A, 2005. Does Trypanosoma cruzi calreticulin modulate the complement system and angiogenesis? Trends Parasitol 21: 169174.

    • Search Google Scholar
    • Export Citation
  • 11.

    Reid KB, Porter RR, 1981. The proteolytic activation systems of complement. Annu Rev Biochem 50: 433464.

  • 12.

    Fujita T, Matsushita M, Endo Y, 2004. The lectin-complement pathway - its role in innate immunity and evolution. Immunol Rev 198: 185202.

  • 13.

    Matsushita M, Fujita T, 1992. Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease. J Exp Med 176: 14971502.

    • Search Google Scholar
    • Export Citation
  • 14.

    Thiel S, Vorup-Jensen T, Stover CM, Schwaeble W, Laursen SB, Poulsen K, Willis AC, Eggleton P, Hansen S, Holmskov U, Reid KB, Jensenius JC, 1997. A second serine protease associated with mannan-binding lectin that activates complement. Nature 386: 506510.

    • Search Google Scholar
    • Export Citation
  • 15.

    Stover CM, Thiel S, Lynch NJ, Schwaeble WJ, 1999. The rat and mouse homologues of MASP-2 and MAp19, components of the lectin activation pathway of complement. J Immunol 163: 68486859.

    • Search Google Scholar
    • Export Citation
  • 16.

    Dahl MR, Thiel S, Matsushita M, Fujita T, Willis AC, Christensen T, Vorup-Jensen T, Jensenius JC, 2001. MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway. Immunity 15: 127135.

    • Search Google Scholar
    • Export Citation
  • 17.

    Henriksen ML, Brandt J, Andrieu JP, Nielsen C, Jensen PH, Holmskov U, Jorgensen TJ, Palarasah Y, Thielens NM, Hansen S, 2013. Heteromeric complexes of native collectin kidney 1 and collectin liver 1 are found in the circulation with MASPs and activate the complement system. J Immunol 191: 61176127.

    • Search Google Scholar
    • Export Citation
  • 18.

    Vorup-Jensen T, Petersen SV, Hansen AG, Poulsen K, Schwaeble W, Sim RB, Reid KB, Davis SJ, Thiel S, Jensenius JC, 2000. Distinct pathways of mannan-binding lectin (MBL)- and C1-complex autoactivation revealed by reconstitution of MBL with recombinant MBL-associated serine protease-2. J Immunol 165: 20932100.

    • Search Google Scholar
    • Export Citation
  • 19.

    Thiel S, Petersen SV, Vorup-Jensen T, Matsushita M, Fujita T, Stover CM, Schwaeble WJ, Jensenius JC, 2000. Interaction of C1q and mannan-binding lectin (MBL) with C1r, C1s, MBL-associated serine proteases 1 and 2, and the MBL-associated protein MAp19. J Immunol 165: 878887.

    • Search Google Scholar
    • Export Citation
  • 20.

    Rossi V, Cseh S, Bally I, Thielens NM, Jensenius JC, Arlaud GJ, 2001. Substrate specificities of recombinant mannan-binding lectin associated serine proteases-1 and -2. J Biol Chem 276: 4088040887.

    • Search Google Scholar
    • Export Citation
  • 21.

    Takahashi M, Iwaki D, Kanno K, Ishida Y, Xiong J, Matsushita M, Endo Y, Miura S, Ishii N, Sugamura K, Fujita T, 2008. Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 contributes to activation of the lectin complement pathway. J Immunol 180: 61326138.

    • Search Google Scholar
    • Export Citation
  • 22.

    Schwaeble WJ, Lynch NJ, Clark JE, Marber M, Samani NJ, Ali YM, Dudler T, Parent B, Lhotta K, Wallis R, Farrar CA, Sacks S, Lee H, Zhang M, Iwaki D, Takahashi M, Fujita T, Tedford CE, Stover CM, 2011. Targeting of mannan-binding lectin-associated serine protease-2 confers protection from myocardial and gastrointestinal ischemia/reperfusion injury. Proc Natl Acad Sci USA 108: 75237528.

    • Search Google Scholar
    • Export Citation
  • 23.

    Turner MW, 2003. The role of mannose-binding lectin in health and disease. Mol Immunol 40: 423429.

  • 24.

    Thiel S, Frederiksen PD, Jensenius JC, 2006. Clinical manifestations of mannan-binding lectin deficiency. Mol Immunol 43: 8696.

  • 25.

    Ram S, Lewis LA, Rice PA, 2010. Infections of people with complement deficiencies and patients who have undergone splenectomy. Clin Microbiol Rev 23: 740780.

    • Search Google Scholar
    • Export Citation
  • 26.

    Evans-Osses I, de Messias-Reason I, Ramirez MI, 2013. The emerging role of complement lectin pathway in trypanosomatids: molecular bases in activation, genetic deficiencies, susceptibility to infection, and complement system-based therapeutics. Scientific World Journal 2013: 112.

    • Search Google Scholar
    • Export Citation
  • 27.

    Cestari I, Evans-Osses I, Schlapbach LJ, de Messias-Reason I, Ramirez MI, 2013. Mechanisms of complement lectin pathway activation and resistance by trypanosomatid parasites. Mol Immunol 53: 328334.

    • Search Google Scholar
    • Export Citation
  • 28.

    Stengaard-Pedersen K, Thiel S, Gadjeva M, Møller-Kristensen M, Sørensen R, Jensen LT, Sjøholm AG, Fugger L, Jensenius JC, 2003. Inherited deficiency of mannan-binding lectin-associated serine protease 2. N Engl J Med 349: 554560.

    • Search Google Scholar
    • Export Citation
  • 29.

    Sørensen R, Thiel S, Jensenius JC, 2005. Mannan-binding lectin-associated serine proteases, characteristics and disease associations. Springer Semin Immun 27: 299319.

    • Search Google Scholar
    • Export Citation
  • 30.

    Cestari I, Krarup A, Sim RB, Inal JM, Ramirez MI, 2009. Role of early lectin pathway activation in the complement-mediated killing of Trypanosoma cruzi. Mol Immunol 47: 426437.

    • Search Google Scholar
    • Export Citation
  • 31.

    Cestari I, Ramirez MI, 2010. Inefficient complement system clearance of Trypanosoma cruzi metacyclic trypomastigotes enables resistant strains to invade eukaryotic cells. PLoS ONE 5: e9721.

    • Search Google Scholar
    • Export Citation
  • 32.

    Shi L, Takahashi K, Dundee J, Shahroor-Karni S, Thiel S, Jensenius JC, Gad F, Hamblin MR, Sastry KN, Ezekowitz RAB, 2004. Mannose-binding lectin-deficient mice are susceptible to infection with Staphylococcus aureus. J Exp Med 199: 13791390.

    • Search Google Scholar
    • Export Citation
  • 33.

    Rothfuchs AG, Roffê E, Gibson A, Cheever AW, Ezekowitz RA, Takahashi K, Steindel M, Sher A, Báfica A, 2012. Mannose-binding lectin regulates host resistance and pathology during experimental infection with Trypanosoma cruzi. PLoS ONE 7: e47835.

    • Search Google Scholar
    • Export Citation
  • 34.

    Ali YM, Lynch NJ, Haleem KS, Fujita T, Endo Y, Hansen S, Holmskov U, Takahashi K, Stahl GL, Dudler T, Girija UV, Wallis R, Kadioglu A, Stover CM, Andrew PW, Schwaeble WJ, 2012. The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection. PLoS Pathog 8: e1002793.

    • Search Google Scholar
    • Export Citation
  • 35.

    Endo Y, Takahashi M, Iwaki D, Ishida Y, Nakazawa N, Kodama T, Matsuzaka T, Kanno K, Liu Y, Tsuchiya K, Kawamura I, Ikawa M, Waguri S, Wada I, Matsushita M, Schwaeble WJ, Fujita T, 2012. Mice deficient in ficolin, a lectin complement pathway recognition molecule, are susceptible to Streptococcus pneumoniae infection. J Immunol 189: 58605866.

    • Search Google Scholar
    • Export Citation
  • 36.

    Roggero E, Perez A, Tamae-Kakazu M, Piazzon I, Nepomnaschy I, Wietzerbin J, Serra E, Revelli S, Bottasso O, 2002. Differential susceptibility to acute Trypanosoma cruzi infection in BALB/c and C57BL/6 mice is not associated with a distinct parasite load but cytokine abnormalities. Clin Exp Immunol 128: 421428.

    • Search Google Scholar
    • Export Citation
  • 37.

    Brener Z, 1962. Therapeutic activity and criterion of cure on mice experimentally infected with Trypanosoma cruzi. Rev Inst Med Trop Sao Paulo 4: 389396.

    • Search Google Scholar
    • Export Citation
  • 38.

    Vespa GN, Cunha FQ, Silva JS, 1994. Nitric oxide is involved in control of Trypanosoma cruzi-induced parasitemia and directly kills the parasite in vitro. Infect Immun 62: 51775182.

    • Search Google Scholar
    • Export Citation
  • 39.

    Krettli AU, Brener Z, 1982. Resistance against Trypanosoma cruzi associated to anti-living trypomastigote antibodies. J Immunol 128: 20092012.

    • Search Google Scholar
    • Export Citation
  • 40.

    Gazzinelli RT, Pereira ME, Romanha A, Gazzinelli G, Brener Z, 1991. Direct lysis of Trypanosoma cruzi: a novel effector mechanism of protection mediated by human anti-gal antibodies. Parasite Immunol 13: 345356.

    • Search Google Scholar
    • Export Citation
  • 41.

    Boldt AB, Luz PR, Messias-Reason IJ, 2011. MASP2 haplotypes are associated with high risk of cardiomyopathy in chronic Chagas disease. Clin Immunol 140: 6370.

    • Search Google Scholar
    • Export Citation
  • 42.

    Pena DA, Eger I, Nogueira L, Heck N, Menin A, Báfica A, Steindel M, 2011. Selection of TcII Trypanosoma cruzi population following macrophage infection. J Infect Dis 204: 478486.

    • Search Google Scholar
    • Export Citation

 

 

 

 

Deficiency in Mannose-Binding Lectin-Associated Serine Protease-2 Does Not Increase Susceptibility to Trypanosoma cruzi Infection

View More View Less
  • Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile; Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom; Department of Microbiology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt

Trypanosoma cruzi is the causative agent of Chagas' disease, a chronic illness affecting 10 million people around the world. The complement system plays an important role in fighting microbial infections. The recognition molecules of the lectin pathway of complement activation, mannose-binding lectin (MBL), ficolins, and CL-11, bind to specific carbohydrates on pathogens, triggering complement activation through MBL-associated serine protease-2 (MASP-2). Previous in vitro work showed that human MBL and ficolins contribute to T. cruzi lysis. However, MBL-deficient mice are only moderately compromised in their defense against the parasite, as they may still activate the lectin pathway through ficolins and CL-11. Here, we assessed MASP-2-deficient mice, the only presently available mouse line with total lectin pathway deficiency, for a phenotype in T. cruzi infection. Total absence of lectin pathway functional activity did not confer higher susceptibility to T. cruzi infection, suggesting that it plays a minor role in the immune response against this parasite.

Author Notes

* Address correspondence to Carolina H. Ribeiro, Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Avenida Independencia 1027, Independencia, Santiago, Chile. E-mail: chager@med.uchile.cl† These authors contributed equally to this article.

Financial support: This work was supported by grants 1130099 from Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) and PIA ACT 112 to AF, and grant G0801952 from the UK Medical Research Council awarded to WJS.

Disclosure: None of the authors has any conflicts of interest.

Authors' addresses: Carolina H. Ribeiro, Carolina Valck, Francisca Noya-Leal, and Arturo Ferreira, Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile, E-mails: chager@med.uchile.cl, cvalck@med.uchile.cl, panchinoya@ug.uchile.cl, and aferreir@med.uchile.cl. Nicholas J. Lynch, Cordula M. Stover, and Wilhelm J. Schwaeble, Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester, UK, E-mails: njl12@le.ac.uk, cms13@le.ac.uk, and ws5@le.ac.uk. Youssif M. Ali, Department of Microbiology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt, E-mail: M_youssif@mans.edu.eg.

Save