期刊论文详细信息
Particle and Fibre Toxicology
Inflammatory responses and intestinal injury development during acute Trypanosoma cruzi infection are associated with the parasite load
Javier Emílio Lazo Chica1  Carlo José Freire de Oliveira2  Maria Tays Mendes2  Wellington Francisco Rodrigues1  Camila Botelho Miguel1  Thaís Perez Vazquez1  Bruna Perez Vazquez1 
[1] Disciplina de Biologia Celular/Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba 38061-500, Minas Gerais, Brazil;Curso de Pós-Graduação em Medicina Tropical e Infectologia, Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais, 38015-050, Brasil
关键词: Inflammation;    Intestinal injury;    Parasite load;    Chagas disease;    T. Cruzi;   
Others  :  1172305
DOI  :  10.1186/s13071-015-0811-8
 received in 2014-09-23, accepted in 2015-03-17,  发布年份 2015
PDF
【 摘 要 】

Background

Chagas disease is caused by the protozoan Trypanosoma cruzi and is characterized by cardiac, gastrointestinal, and nervous system disorders. Although much about the pathophysiological process of Chagas disease is already known, the influence of the parasite burden on the inflammatory process and disease progression remains uncertain.

Methods

We used an acute experimental disease model to evaluate the effect of T. cruzi on intestinal lesions and assessed correlations between parasite load and inflammation and intestinal injury at 7 and 14 days post-infection. Low (3 × 102), medium (3 × 103), and high (3 × 104) parasite loads were generated by infecting C57BL/6 mice with “Y”-strain trypomastigotes. Statistical analysis was performed using analysis of variance with Tukey’s multiple comparison post-test, Kruskal–Wallis test with Dunn’s multiple comparison, χ2 test and Spearman correlation.

Results

High parasite load-bearing mice more rapidly and strongly developed parasitemia. Increased colon width, inflammatory infiltration, myositis, periganglionitis, ganglionitis, pro-inflammatory cytokines (e.g., TNF-α, INF-γ, IL-2, IL-17, IL-6), and intestinal amastigote nests were more pronounced in high parasite load-bearing animals. These results were remarkable because a positive correlation was observed between parasite load, inflammatory infiltrate, amastigote nests, and investigated cytokines.

Conclusions

These experimental data support the idea that the parasite load considerably influences the T. cruzi-induced intestinal inflammatory response and contributes to the development of the digestive form of the disease.

【 授权许可】

   
2015 Vazquez et al.; licensee BioMed Central.

【 预 览 】
附件列表
Files Size Format View
20150421090023197.pdf 1759KB PDF download
Figure 6. 61KB Image download
Figure 5. 57KB Image download
Figure 4. 33KB Image download
Figure 3. 115KB Image download
Figure 2. 82KB Image download
Figure 1. 22KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】
  • [1]Chagas C. Nova tripanozomiaze 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. 1909; 1(2):159-218.
  • [2]Steverding D. The history of Chagas disease. Parasites vectors. 2014; 7(1):317. BioMed Central Full Text
  • [3]Pereira PCM, Navarro EC. Challenges and perspectives of Chagas disease: a review. J Venomous Animals Toxins Including Trop Dis. 2013; 19(1):34. BioMed Central Full Text
  • [4]Macedo AM, Machado CR, Oliveira RP, Pena SD. Trypanosoma cruzi: genetic structure of populations and relevance of genetic variability to the pathogenesis of Chagas disease. Mem Inst Oswaldo Cruz. 2004; 99(1):1-12.
  • [5]Prata A. Classificação da infecção chagásica no homem. Rev Soc Bras Med Trop. 1990; 23(2):109-13.
  • [6]Freire-de-Lima CG, Nascimento DO, Soares MB, Bozza PT, Castro-Faria-Neto HC, de Mello FG et al.. Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages. Nature. 2000; 403(6766):199-203.
  • [7]Chapadeiro E. Clinical evolution and morbi-mortality in Chagas disease. MEMORIAS-INSTITUTO OSWALDO CRUZ. 1999; 94:309-10.
  • [8]Prata A. Clinical and epidemiological aspects of Chagas disease. Lancet Infect Dis. 2001; 1(2):92-100.
  • [9]Pallisera A, Ortiz-de-Zárate L, Moral A, Rey F, Lopez S, López M et al.. Chagas disease in the differential diagnosis of megacolon. Revista española de enfermedades digestivas: organo oficial de la Sociedad Española de Patología Digestiva. 2011; 103(10):554.
  • [10]Köberle F. Chagas' disease and Chagas' syndromes: the pathology of American trypanosomiasis. Adv Parasitol. 1968; 6:63-116.
  • [11]Adad SJ, Cançado CG, Etchebehere RM, Teixeira VP, Gomes UA, Chapadeiro E et al.. Neuron count reevaluation in the myenteric plexus of chagasic megacolon after morphometric neuron analysis. Virchows Arch. 2001; 438(3):254-8.
  • [12]Arantes RM, Marche HH, Bahia MT, Cunha FQ, Rossi MA, Silva JS. Interferon-γ-Induced Nitric Oxide Causes Intrinsic Intestinal Denervation in Trypanosoma cruzi−Infected Mice. Am J Pathol. 2004; 164(4):1361-8.
  • [13]Lopes GP, Ferreira-Silva MM, Ramos AA, Moraes-Souza H, Prata A, Correia D. Length and caliber of the rectosigmoid colon among patients with Chagas disease and controls from areas at different altitudes. Rev Soc Bras Med Trop. 2013; 46(6):746-51.
  • [14]Moreira NM, Sant'Ana DM, Araújo EJ, Toledo MJ, Gomes ML, Araújo SM. Neuronal changes caused by Trypanosoma cruzi: an experimental model. An Acad Bras Cienc. 2011; 83(2):545-55.
  • [15]Lemos JRD, Rodrigues WF, Miguel CB, Parreira RC, Miguel RB, de Paula RA et al.. Influence of Parasite Load on Renal Function in Mice Acutely Infected with Trypanosoma cruzi. PLoS One. 2013; 8(8):e71772.
  • [16]Borges DC, Araújo NM, Cardoso CR, Lazo Chica JE. Different parasite inocula determine the modulation of the immune response and outcome of experimental Trypanosoma cruzi infection. Immunology. 2013; 138(2):145-56.
  • [17]Meza SKL, Kaneshima EN, de Oliveira SS, Gabriel M, de Araújo SM, Gomes ML et al.. Comparative pathogenicity in Swiss mice of Trypanosoma cruzi IV from northern Brazil and Trypanosoma cruzi II from southern Brazil. Exp Parasitol. 2014; 146:34-42.
  • [18]Zingales B, Andrade SG, Briones M, Campbell D, Chiari E, Fernandes O et al.. A new consensus for Trypanosoma cruzi intraspecific nomenclature: second revision meeting recommends TcI to TcVI. Mem Inst Oswaldo Cruz. 2009; 104(7):1051-4.
  • [19]Higuera SL, Guhl F, Ramírez JD. Identification of Trypanosoma cruzi Discrete Typing Units (DTUs) through the implementation of a High-Resolution Melting (HRM) genotyping assay. Parasites Vectors. 2013; 6(1):112. BioMed Central Full Text
  • [20]Silva L, Nussenzweig V. Sobre uma cepa de Trypanosoma cruzi altamente virulenta para o camundongo branco. Folia clin biol. 1953; 20(191–267):29.
  • [21]Andrade SG, Magalhães JB. Biodemes and zymodemes of Trypanosoma cruzi strains: correlations with clinical data and experimental pathology. Rev Soc Bras Med Trop. 1997; 30(1):27-35.
  • [22]Brener Z. Therapeutic activity and criterion of cure on mice experimentally infected with Trypanosoma cruzi. Rev Inst Med Trop Sao Paulo. 1962; 4(11–12):389-96.
  • [23]Marinho CR, Lima MRDI, Grisotto MG, Alvarez JM. Influence of acute-phase parasite load on pathology, parasitism, and activation of the immune system at the late chronic phase of Chagas’ disease. Infect Immun. 1999; 67(1):308-18.
  • [24]Moreno E, Añez N, Scorza C, Lugo de Yarbuh A, Borges R. Efecto de inóculos bajos en la infección experimental por Trypanosoma cruzi. Malariol San Amb. 1999; 39:1-9.
  • [25]Todd I, Porter N, Morson B, Smith B, Friedmann C, Neal R. Chagas disease of the colon and rectum. Gut. 1969; 10(12):1009-14.
  • [26]Fernandes M, Zucoloto S, Collares E, Ferriolli Filho F. Morphometric investigations of the colon mucosa in chronicTrypanosoma cruzi infected rats. Virchows Archiv B. 1991; 60(1):119-22.
  • [27]Ny L, Li H, Mukherjee S, Persson K, Holmqvist B, Zhao D et al.. A magnetic resonance imaging study of intestinal dilation in Trypanosoma cruzi–infected mice deficient in nitric oxide synthase. Am J Trop Med Hyg. 2008; 79(5):760-7.
  • [28]Nogueira-Paiva NC, Fonseca KS, Vieira PMA, Diniz LF, Caldas IS, Moura SAL et al.. Myenteric plexus is differentially affected by infection with distinct Trypanosoma cruzi strains in Beagle dogs. Memórias do Instituto Oswaldo Cruz. 2014; 109(1):51-60.
  • [29]Côbo EdC, Silveira TP, Micheletti AM, Crema E, Adad SJ: Research on Trypanosoma cruzi and analysis of inflammatory infiltrate in esophagus and colon from chronic chagasic patients with and without mega. Journal of tropical medicine 2012, 232646
  • [30]da Matta Guedes PM, Gutierrez FR, Maia FL, Milanezi CM, Silva GK, Pavanelli WR et al.. IL-17 produced during Trypanosoma cruzi infection plays a central role in regulating parasite-induced myocarditis. PLoS Negl Trop Dis. 2010; 4(2):e604.
  • [31]Miyazaki Y, Hamano S, Wang S, Shimanoe Y, Iwakura Y, Yoshida H. IL-17 is necessary for host protection against acute-phase Trypanosoma cruzi infection. The J Immunology. 2010; 185(2):1150-7.
  • [32]Magalhães LM, Villani FN, Maria do Carmo PN, Gollob KJ, Rocha MO, Dutra WO: High interleukin 17 expression is correlated with better cardiac function in human Chagas disease. Journal of Infectious Diseases 2012:jis724.
  • [33]Sousa GR, Gomes JAS, Fares RCG, de Souza Damásio MP, Chaves AT, Ferreira KS et al.. Plasma Cytokine Expression Is Associated with Cardiac Morbidity in Chagas Disease. PLoS One. 2014; 9(3):e87082.
  • [34]Nabors GS, Tarleton RL. Differential control of IFN-gamma and IL-2 production during Trypanosoma cruzi infection. The J Immunology. 1991; 146(10):3591-8.
  • [35]Silva J, Morrissey P, Grabstein K, Mohler K, Anderson D, Reed S. Interleukin 10 and interferon gamma regulation of experimental Trypanosoma cruzi infection. J Exp Med. 1992; 175(1):169-74.
  • [36]Eksi S, Wassom DL, Powell MR. Host genetics and resistance to acute Trypanosoma cruzi infection in mice: profiles and compartmentalization of IL-2-,-4-,-5-,-10-, and IFN-γ-producing cells. J Parasitol. 1996; 82(1):59-65.
  • [37]Abrahamsohn IA, Coffman RL. Trypanosoma cruzi:IL-10, TNF, IFN-γ, and IL-12 Regulate Innate and Acquired Immunity to Infection. Exp Parasitol. 1996; 84(2):231-44.
  • [38]Pissetti CW, Correia D, De Oliveira RF, Llaguno MM, Balarin MAS, Silva-Grecco RL et al.. Genetic and functional role of TNF-alpha in the development Trypanosoma cruzi infection. PLoS Negl Trop Dis. 2011; 5(3):e976.
  • [39]D'Ávila DA, Guedes PM, Castro AM, Gontijo ED, Chiari E, Galvão L. Immunological imbalance between IFN-3 and IL-10 levels in the sera of patients with the cardiac form of Chagas disease. Mem Inst Oswaldo Cruz. 2009; 104(1):100-5.
  • [40]Guedes PMM, Gutierrez FRS, Silva GK, Dellalibera-Joviliano R, Rodrigues GJ, Bendhack LM et al.. Deficient regulatory T cell activity and low frequency of IL-17-producing T cells correlate with the extent of cardiomyopathy in human Chagas' disease. PLoS Negl Trop Dis. 2012; 6(4):e1630.
  • [41]Machado FS, Dutra WO, Esper L, Gollob KJ, Teixeira MM, Factor SM et al.. Current understanding of immunity to Trypanosoma cruzi infection and pathogenesis of Chagas disease. Seminars immunopathology. 2012; 34(6):753-70.
  • [42]Hunter CA, Ellis-Neyes LA, Slifer T, Kanaly S, Grünig G, Fort M et al.. IL-10 is required to prevent immune hyperactivity during infection with Trypanosoma cruzi. J Immunology. 1997; 158(7):3311-6.
  • [43]Tarleton RL, Grusby MJ, Postan M, Glimcher LH. Trypanosoma cruzi infection in MHC-deficient mice: further evidence for the role of both class I-and class II-restricted T cells in immune resistance and disease. Int Immunol. 1996; 8(1):13-22.
  • [44]Cencig S, Coltel N, Truyens C, Carlier Y. Parasitic loads in tissues of mice infected with Trypanosoma cruzi and treated with Am Bisome. PLoS Negl Trop Dis. 2011; 5(6):e1216.
  • [45]Rossi MA. Pathogenesis of chronic Chagas' myocarditis. Sao Paulo Med J. 1995; 113(2):750-6.
  • [46]Martins-Melo FR, Ramos AN, Alencar CH, Heukelbach J. Mortality related to Chagas disease and HIV/AIDS coinfection in Brazil. J Tropical Med. 2012; 2012(534649):1-4.
  • [47]Altclas J, Sinagra A, Dictar M, Luna C, Veron M, De Rissio A et al.. Chagas disease in bone marrow transplantation: an approach to preemptive therapy. Bone Marrow Transplant. 2005; 36(2):123-9.
  • [48]Querido JF, Echeverría MG, Marti GA, Costa RM, Susevich ML, Rabinovich JE et al.. Seroprevalence of Triatoma virus (Dicistroviridae: Cripaviridae) antibodies in Chagas disease patients. Parasites Vectors. 2015; 8(1):29. BioMed Central Full Text
  文献评价指标  
  下载次数:0次 浏览次数:3次