Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 119 | 2024
Research Articles
Revisiting the development of Trypanosoma rangeli in the vertebrate host
1Fundação Oswaldo Cruz-Fiocruz, Instituto René Rachou, Grupo de Comportamento de Vetores e Interação com Patógenos, Belo Horizonte, MG, Brasil
2Fundação Oswaldo Cruz-Fiocruz, Instituto René Rachou, Grupo de Biotecnologia Aplicada ao Estudo de Patógenos, Belo Horizonte, MG, Brasil
3Instituto de Investigaciones en Biodiversidad y Biotecnología, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Mar del Plata, Argentina
DOI: 10.1590/0074-02760240138
ABSTRACT
BACKGROUND Trypanosoma rangeli is a haemoflagellate parasite that infects triatomine bugs and mammals in South and Central America. Trypanosoma cruzi, the etiological agent of Chagas disease, has a partially overlapping geographical distribution with T. rangeli, that leads to mixed human infections and cross-reactivity in immunodiagnosis. Although T. rangeli can be detected long after mammal infection, its multiplicative forms have not yet been described.
OBJECTIVES To enhance our understanding of T. rangeli development in mammals, this study assessed various infection parameters in mice over time.
METHODS The parasitaemia, body temperature, and weight of Swiss Webster mice were monitored over 120 days after exposing them to the bites of Rhodnius prolixus nymphs containing metacyclic trypomastigotes in their salivary glands. On day 132 post-infection, spleens and mesenteric lymph nodes were analysed for T. rangeli DNA using polymerase chain reaction (PCR) and quantitative PCR (qPCR).
FINDINGS Parasites were detectable in mice blood since day 2 post-infection, detection peaking on day 5 and becoming undetectable by day 120. PCR and qPCR detected T. rangeli DNA in the spleens and mesenteric lymph nodes of infected mice. Infected mice showed higher body temperatures and a slower weight gain over time compared to controls.
MAIN CONCLUSIONS The study confirmed that T. rangeli establishes a persistent infection in mice, detectable in lymphoid organs long after parasites had disappeared from blood. In addition, infected mice exhibited physiological changes, suggesting potential subclinical effects. These findings highlight the need for further studies on the immune response and potential impacts of T. rangeli infection in mammalian hosts.
REFERENCES
01. Grisard EC, Steindel M, Guarneri AA, Eger-Mangrich I, Campbell DA, Romanha AJ. Characterization of Trypanosoma rangeli strains isolated in Central and South America: an overview. Mem Inst Oswaldo Cruz. 1999; 94(2): 203-9.
02. Sincero TCM, Stoco PH, Steindel M, Vallejo GA, Grisard EC. Trypanosoma rangeli displays a clonal population structure, revealing a subdivision of KP1 (−) strains and the ancestry of the Amazonian group. Int J Parasitol. 2015; 45(4): 225-35.
03. Vallejo GA, Guhl F, Carranza JC, Moreno J, Triana O, Grisard EC. Parity between kinetoplast DNA and mini-exon gene sequences supports either clonal evolution or speciation in Trypanosoma rangeli strains isolated from Rhodnius colombiensis, R. pallescens and R. prolixus in Colombia. Infect Genet Evol. 2003; 3(1): 39-45.
04. Maia Da Silva F, Junqueira ACV, Campaner M, Rodrigues AC, Crisante G, Ramirez LE, et al. Comparative phylogeography of Trypanosoma rangeli and Rhodnius (Hemiptera: Reduviidae) supports a long coexistence of parasite lineages and their sympatric vectors. Mol Ecol. 2007; 16(16): 3361-73.
05. Urrea DA, Guhl F, Herrera CP, Falla A, Carranza JC, Cuba-Cuba C, et al. Sequence analysis of the spliced-leader intergenic region (SL-IR) and random amplified polymorphic DNA (RAPD) of Trypanosoma rangeli strains isolated from Rhodnius ecuadoriensis, R. colombiensis, R. pallescens and R. prolixus suggests a degree of co-evolution between parasites and vectors. Acta Trop. 2011; 120(1-2): 59-66.
06. Guhl F, Hudson L, Marinkelle CJ, Jaramillo CA, Bridge D. Clinical Trypanosoma rangeli infection as a complication of Chagas’ disease. Parasitology. 1987; 94(3): 475-84.
07. Pavia PX, Vallejo GA, Montilla M, Nicholls RS, Puerta CJ. Detection of Trypanosoma cruzi and Trypanosoma rangeli infection in triatomine vectors by amplification of the histone H2A/SIRE and the sno- RNA-C11 genes. Rev Inst Med Trop São Paulo. 2007; 49: 23-30.
08. Araujo VAL, Boite MC, Cupolillo E, Jansen AM, Roque ALR. Mixed infection in the anteater Tamandua tetradactyla (Mammalia: Pilosa) from Pará State, Brazil: Trypanosoma cruzi, T. rangeli and Leishmania infantum. Parasitology. 2013; 140(4): 455-60.
09. Afchain D, Le Ray D, Fruit J, Capron A. Antigenic make-up of Trypanosoma cruzi culture forms: Identification of a specific component. J Parasitol. 1979; 65: 314-507.
10. Guhl F, Marinkelle CJ. Antibodies against Trypanosoma cruzi in mice infected with T. rangeli. Ann Trop Med Parasitol. 1982; 76: 361.
11. O’Daly JA, Carrasco H, Fernandez V, Rodriguez MB. Comparison of chagasic and non-chagasic myocardiopathies by ELISA and immunoblotting with antigens of Trypanosoma cruzi and Trypanosoma rangeli. Acta Trop. 1994; 56: 265-87.
12. Moraes MH, Guarneri AA, Girardi FP, Rodrigues JB, Eger I, Tyler KM, et al. Different serological cross-reactivity of Trypanosoma rangeli forms in Trypanosoma cruzi-infected patients sera. Parasit Vectors. 2008; 1: 1-10.
13. Schottelius J. Neuraminidase fluorescence test for the differentiation of Trypanosoma cruzi and Trypanosoma rangeli. Trop Med Parasitol. 1987; 38(4): 323-7.
14. Guhl F, Vallejo GA. Trypanosoma (Herpetosoma) rangeli Tejera, 1920 - An updated review. Mem Inst Oswaldo Cruz. 2003; 98(4): 435-42.
15. Guarneri AA, Lorenzo MG. Triatomine physiology in the context of trypanosome infection. J Insect Physiol. 2017; 97: 66-76.
16. Ferreira RC, Teixeira CF, de Sousa VFA, Guarneri AA. Effect of temperature and vector nutrition on the development and multiplication of Trypanosoma rangeli in Rhodnius prolixus. Parasitol Res. 2018; 117(6): 1737-44.
17. D’Alessandro A. Biology of Trypanosoma (Herpetosoma) rangeli Tejera, 1920. Biol Kinetoplastida. 1976; 328-403.
18. Molyneux D. Division of the human trypanosome, Trypanosoma (Herpetosoma) rangeli. Ann Trop Med Parasitol. 1973; 67(3): 371-2.
19. Osorio Y, Travi BL, Palma GI, Saravia NG. Infectivity of Trypanosoma rangeli in a promonocytic mammalian cell line. J Parasitol. 1995; 687-93.
20. Eger-Mangrich I, Oliveira M, Grisard EC, Souza W, Steindel M. Interaction of Trypanosoma rangeli Tejera, 1920 with different cell lines in vitro. Parasitol Res. 2001; 87(6): 505-9.
21. Ferreira LL, Araujo FF, Martinelli PM, Teixeira-Carvalho A, Alves-Silva J, Guarneri AA. New features on the survival of human- infective Trypanosoma rangeli in a murine model: parasite accumulation is observed in lymphoid organs. PLoS Negl Trop Dis. 2020; 14(12): e0009015.
22. Dario MA, Pavan MG, Rodrigues MS, Lisboa CV, Kluyber D, Desbiez AL, et al. Trypanosoma rangeli genetic, mammalian hosts, and geographical diversity from five Brazilian biomes. Pathogens. 2021; 10(6): 736.
23. Maia Da Silva F, Noyes H, Campaner M, Junqueira ACV, Coura JR, Añez N, et al. Phylogeny, taxonomy and grouping of Trypanosoma rangeli isolates from man, triatomines and sylvatic mammals from widespread geographical origin based on SSU and ITS ribosomal sequences. Parasitology. 2004; 129(5): 549-61.
24. Parada C, Villalba J, Alvarez M, Puig N, Planelles D, Ramada C, et al. Trypanosoma rangeli in a blood donor at the Valencian Blood Transfusion Centre. Vox Sang. 2010; 99(2): 193.
25. Rodrigues JDO, Lorenzo MG, Martins-Filho OA, Elliot SL, Guarneri AA. Temperature and parasite life-history are important modulators of the outcome of Trypanosoma rangeli–Rhodnius prolixus interactions. Parasitology. 2016; 143(11): 1459-68.
26. Brener Z. Therapeutic activity and criterion of cure of mice experimentally infected with Trypanosoma cruzi. Rev Inst Med Trop São Paulo. 1962; 4(6): 389-96.
27. Diez H, Thomas MC, Uruena CP, Santander SP, Cuervo CL, López MC, et al. Molecular characterization of the kinetoplastid membrane protein-11 genes from the parasite Trypanosoma rangeli. Parasitology. 2005; 130(6): 643-51.
28. Herbig-Sandreuter A. Experimental investigation of the life-cycle of Trypanosoma rangeli in warm blooded animals and in Rhodnius prolixus. Acta Trop. 1955; 12(3): 261-4.
29. Urdaneta-Morales S, Tejero F. Trypanosoma (Herpetosoma) rangeli Tejera, 1920: mouse model for high, sustained parasitemia. J Parasitol. 1985; 71(4): 409-14.
30. Scorza C, Urdaneta-Morales S, Tejero F. Trypanosoma (Herpetosoma) rangeli Tejera, 1920: preliminary report on histopathology in experimentally infected mice. Rev Inst Med Trop São Paulo. 1986; 28(5): 371-8.
31. Tanoura K, Yanagi T, Garcia VMD, Kanbara H. Trypanosoma rangeli — In vitro metacyclogenesis and fate of metacyclic trypomastigotes after infection to mice and fibroblast cultures. J Eukaryot Microbiol. 1999; 46(1): 43-8.
32. Soares MB, Titus RG, Shoemaker CB, David JR, Bozza M. The vasoactive peptide maxadilan from sand fly saliva inhibits TNF-α and induces IL-6 by mouse macrophages through interaction with the pituitary adenylate cyclase-activating polypeptide (PACAP). J Immunol. 1998; 160(4): 1811-6.
33. Qureshi AA, Asahina A, Ohnuma M, Tajima M, Granstein RD, Lerner EA. Immunomodulatory properties of maxadilan, the vasodilator peptide from sand fly salivary gland extracts. Am J Trop Med Hyg. 1996; 54(6): 665-71.
34. Schneider CA, Calvo E, Peterson KE. Arboviruses: how saliva impacts the journey from vector to host. Int J Mol Sci. 2021; 22(17): 9173.
35. Arora G, Chuang YM, Sinnis P, Dimopoulos G, Fikrig E. Malaria: influence of Anopheles mosquito saliva on Plasmodium infection. Trends Immunol. 2023; 44(4): 256-65.
36. Ramamoorthi N, Narasimhan S, Pal U, Bao F, Yang XF, Fish D, et al. The Lyme disease agent exploits a tick protein to infect the mammalian host. Nature. 2005; 436(7050): 573-7.
37. Añez N, Velandia J, Rodríguez AM. Estudios sobre Trypanosoma rangeli Tejera, 1920. VIII. Respuesta a las reinfecciones en dos mamiferos. Mem Inst Oswaldo Cruz. 1985; 80(2): 149-53.
38. D’Alessandro A, Saravia NG. Trypanosoma rangeli. Parasitic Protozoa. 1992; 2: 1-54.
39. Dario MA, Lisboa CV, Xavier SCDC, D’Andrea PS, Roque ALR, Jansen AM. Trypanosoma species in small nonflying mammals in an area with a single previous Chagas disease case. Front Cell Infect Microbiol. 2022; 12: 812708.
40. Coura J, Fernandes O, Arboleda M, Barrett TV, Carrara N, Degrave W, et al. Human infection by Trypanosoma rangeli in the Brazilian Amazon. Trans R Soc Trop Med Hyg. 1996; 90(3): 278-9.
41. Vergara-Meza JG, Brilhante AF, Valente VDC, Villalba-Alemán E, Ortiz PA, Cosmiro de Oliveira S, et al. Trypanosoma cruzi and Trypanosoma rangeli in Acre, Brazilian Amazonia: coinfection and notable genetic diversity in an outbreak of orally acquired acute Chagas disease in a forest community, wild reservoirs, and vectors. Parasitologia. 2022; 2(4): 350-65.
42. Saldaña A, Samudio F, Miranda A, Herrera LM, Saavedra SP, Cáceres L, et al. Predominance of Trypanosoma rangeli infection in children from a Chagas disease endemic area in the west-shore of the Panama canal. Mem Inst Oswaldo Cruz. 2005; 100(7): 729-31.
43. Basso B, Castro I, Introini V, Gil P, Truyens C, Moretti E. Vaccination with Trypanosoma rangeli reduces the infectiousness of dogs experimentally infected with Trypanosoma cruzi. Vaccine. 2007; 25: 3855-8.
44. Basso B, Moretti E, Fretes R. Vaccination with fixed epimastigotes of different strains of Trypanosoma rangeli protects mice against Trypanosoma cruzi infection. Mem Inst Oswaldo Cruz. 2008; 103(4): 370-4.
45. Basso B, Moretti E, Fretes R. Vaccination with Trypanosoma rangeli induces resistance of guinea pigs to virulent Trypanosoma cruzi. Vet Immunol Immunopathol. 2014; 157: 119-23.
46. Travieso T, Li J, Mahesh S, Mello JD, Blasi M. The use of viral vectors in vaccine development. NPJ Vaccines. 2022; 7(1): 75.
47. Yurina V. Live bacterial vectors-A promising DNA vaccine delivery system. Med Sci. 2018; 6(2): 27.
48. Zou J, Huang XX, Yin GW, Ding Y, Liu XY, Wang H, et al. Evaluation of Toxoplasma gondii as a live vaccine vector in susceptible and resistant hosts. Parasites Vectors. 2011; 4: 1-9.
49. Breton M, Tremblay MJ, Ouellette M, Papadopoulou B. Live nonpathogenic parasitic vector as a candidate vaccine against visceral leishmaniasis. Infect Immun. 2005; 73(10): 6372-82.
50. Junqueira C, Santos LI, Galvão-Filho B, Teixeira SM, Rodrigues FG, DaRocha WD, et al. Trypanosoma cruzi as an effective cancer antigen delivery vector. Proc Natl Acad Sci USA. 2011; 108(49): 19695-700.
51. Avila JL, Rojas M. Elevated cerebroside antibody levels in human visceral and cutaneous leishmaniasis, Trypanosoma rangeli infection, and chronic Chagas’ disease. Am J Trop Med Hyg. 1990; 43(1): 52-60.
52. Guhl F, Hudson L, Marinkelle CJ, Morgan SJ, Jaramillo C. Antibody response to experimental Trypanosoma rangeli infection and its implications for immunodiagnosis of South American trypanosomiasis. Acta Trop. 1985; 42(4): 311-8.
53. Stoco PH, Wagner G, Talavera-Lopez C, Gerber A, Zaha A, Thompson CE, et al. Genome of the avirulent human-infective trypanosome — Trypanosoma rangeli. PLoS Negl Trop Dis. 2014; 8(9): e3176.
54. Costa RW, Batista MF, Meneghelli I, Vidal RO, Najera CA, Mendes AC, et al. Comparative analysis of the secretome and interactome of Trypanosoma cruzi and Trypanosoma rangeli reveals species specific immune response modulating proteins. Front Immunol. 2020; 11: 550289.
Financial support: This study was financed in part by the CAPES (Finance code 001), CNPq productivity grant (to AAG - grant number 304862/2022-3), FAPEMIG (grant numbers PPM-00162-17, APQ-01708-22), INCTEM/CNPq (grant number 465678/2014-9).
+ Corresponding author: alessandra.guarneri@fiocruz.br 
https://orcid.org/0000-0002-9162-2731
Received 29 June 2024
Accepted 30 September 2024
HOW TO CITE:
Santos LF, Rocha FS, Lorenzo MG, Guarneri AA. Revisiting the development of Trypanosoma rangeli in the vertebrate host. Mem Inst Oswaldo Cruz. 2024; 119: e240138.
