Hostname: page-component-cd9895bd7-dzt6s Total loading time: 0 Render date: 2024-12-22T12:25:56.019Z Has data issue: false hasContentIssue false

Impact of collaborative actions of Leishmania (Viannia) braziliensis subpopulations on the infection profile

Published online by Cambridge University Press:  13 July 2022

Barbara Cristina de Albuquerque-Melo
Affiliation:
Laboratório de Biologia Molecular e Doenças Endêmicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil
Léa Cysne-Finkelstein
Affiliation:
Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil
Luiz Filipe Gonçalves-Oliveira
Affiliation:
Laboratório de Biologia Molecular e Doenças Endêmicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil
Cynthia Machado Cascabulho
Affiliation:
Laboratório de Inovação em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil
Andrea Henriques-Pons
Affiliation:
Laboratório de Inovação em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil
Mirian Cláudia de Souza Pereira
Affiliation:
Laboratório de Ultraestrutura Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil
Carlos Roberto Alves*
Affiliation:
Laboratório de Biologia Molecular e Doenças Endêmicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil
Geovane Dias-Lopes
Affiliation:
Laboratório de Biologia Molecular e Doenças Endêmicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil
*
Author for correspondence: Carlos Roberto Alves, E-mail: [email protected]

Abstract

This study focuses on the role of the population structure of Leishmania spp. on the adaptive capacity of the parasite. Herein, we investigate the contribution of subpopulations of the L. (V.) braziliensis Thor strain (Thor03, Thor10 and Thor22) in the profile of murine macrophages infection. Infection assays were performed with binary combinations of these subpopulations at stationary phases. The initial interaction time showed major effects on the combination assays, as demonstrated by the significant increase in the infection rate at 5 h. Based on the endocytic index (EI), Thor10 (EI = 563.6) and Thor03 (EI = 497) showed a higher infection load compared to Thor22 (EI = 227.3). However, the EI decreased in Thor03 after 48 h (EI = 447) and 72 h (EI = 388.3) of infection, and showed changes in the infection level in all Thor10/Thor22 combinations. Assays with CellTrace CFSE-labelled Thor22 promastigotes indicated an increase (~1.5 fold) in infection by this subpopulation in the presence of Thor10 when compared to the infection profile of Thor03/Thor22 combinations in the same proportions. In addition, the potential of these subpopulations, alone or in binary combinations, to modulate the expression of cytokines and nitric oxide (NO) in vitro was investigated. Lower NO and tumour necrosis factor-α production levels were observed for all Thor10/Thor22 combinations at 24 h compared to these subpopulations alone. In contrast, Thor03/Thor22 combination assays increased IL-10 production at this time. Collectively, these results provide in vitro evidence on the potential of L. (V.) braziliensis population structure to play a relevant role in a host infection by this parasite.

Type
Research Article
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Akopyants, NS, Kimblin, N, Secundino, N, Patrick, R, Peters, N, Lawyer, P, Dobson, DE, Beverley, SM and Sacks, DL (2009) Demonstration of genetic exchange during cyclical development of Leishmania in the sand fly vector. Science 324, 265268.CrossRefGoogle ScholarPubMed
Bhattacharyya, A, Mukherjee, M and Duttagupta, S (2002) Studies on Stibanate unresponsive isolates of Leishmania donovani. Journal of Biosciences 27, 503508.CrossRefGoogle ScholarPubMed
Burza, S, Croft, SL and Boelaert, M (2018) Leishmaniasis. Lancet 392, 951970.CrossRefGoogle ScholarPubMed
Chang, HK, Thalhofer, C, Duerkop, BA, Mehling, JS, Verma, S, Gollob, KJ, Almeida, R and Wilson, ME (2007) Oxidant generation by single infected monocytes after short-term fluorescence labeling of a protozoan parasite. Infection and Immunity 75, 10171024.CrossRefGoogle ScholarPubMed
Coelho, AC, Boisvert, S, Mukherjee, A, Leprohon, P, Corbeil, J and Ouellette, M (2012) Multiple mutations in heterogeneous miltefosine-resistant Leishmania major population as determined by whole genome sequencing. PLoS Neglected Tropical Diseases 6, e1512.CrossRefGoogle ScholarPubMed
Cupolillo, E, Grimaldi, G Jr and Momen, H (1997) Genetic diversity among Leishmania (Viannia) parasites. Annals of Tropical Medicine & Parasitology 91, 617626.CrossRefGoogle ScholarPubMed
Cupolillo, E, Momen, H and Grimaldi, G Jr (1998) Genetic diversity in natural populations of New World Leishmania. Memórias do Instituto Oswaldo Cruz 93, 663668.CrossRefGoogle ScholarPubMed
Cupolillo, E, Brahim, LR, Toaldo, CB, de Oliveira-Neto, MP, de Brito, MEF, Falqueto, A and Grimaldi, G Jr (2003) Genetic polymorphism and molecular epidemiology of Leishmania (Viannia) braziliensis from different hosts and geographic areas in Brazil. Journal of Clinical Microbiology 41, 31263132.CrossRefGoogle ScholarPubMed
Cysne-Finkelstein, L, Silva-Almeida, M, Pereira, BAS, dos Santos Charret, K, Bertho, AL, Bastos, LS and Alves, CR (2018) Evidence of subpopulations with distinct biological features within a Leishmania (Viannia) braziliensis strain. Protist 169, 107121.CrossRefGoogle ScholarPubMed
Decuypere, S, Vanaerschot, M, Brunker, K, Imamura, H, Müller, S, Khanal, B, Rijal, S, Dujardin, JC and Coombs, GH (2012) Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background. PLoS Neglected Tropical Diseases 6, e1514.CrossRefGoogle ScholarPubMed
Dumetz, F, Cuypers, B, Imamura, H, Zander, D, D'Haenens, E, Maes, I, Domagalska, MA, Clos, J, Dujardin, JC and De Muylder, G (2018) Molecular preadaptation to antimony resistance in Leishmania donovani on the Indian subcontinent. MSphere 3, e00548–17.CrossRefGoogle ScholarPubMed
Espiau, B, Vilhena, V, Cuvillier, A, Barral, A and Merlin, G (2017) Phenotypic diversity and selection maintain Leishmania amazonensis infectivity in BALB/c mouse model. Memórias do Instituto Oswaldo Cruz 112, 4452.CrossRefGoogle ScholarPubMed
Garin, YJF, Sulahian, A, Pratlong, F, Meneceur, P, Gangneux, JP, Prina, E, Dedet, JP and Derouin, F (2001) Virulence of Leishmania infantum is expressed as a clonal and dominant phenotype in experimental infections. Infection and Immunity 69, 73657373.CrossRefGoogle ScholarPubMed
Gelanew, T, Kuhls, K, Hurissa, Z, Weldegebreal, T, Hailu, W, Kassahun, A, Abebe, T, Hailu, A and Schönian, G (2010) Inference of population structure of Leishmania donovani strains isolated from different Ethiopian visceral leishmaniasis endemic areas. PLoS Neglected Tropical Diseases 4, e889.CrossRefGoogle ScholarPubMed
Giudice, A, Camada, I, Leopoldo, PT, Pereira, JM, Riley, LW, Wilson, ME, Ho, JL, de Jesus, AR, Carvalho, EM and Almeida, RP (2007) Resistance of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis to nitric oxide correlates with disease severity in tegumentary leishmaniasis. BMC Infectious Diseases 7, 7.CrossRefGoogle ScholarPubMed
Gomes, RF, Macedo, AM, Pena, SDJ and Melo, MN (1995) Leishmania (Viannia) braziliensis: genetic relationships between strains isolated from different areas of Brazil as revealed by DNA fingerprinting and RAPD. Experimental Parasitology 80, 681687.CrossRefGoogle ScholarPubMed
Green, LC, Wagner, DA, Glogowski, J, Skipper, PL, Wishnok, JS and Tannenbaum, SR (1982) Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Analytical Biochemistry 126, 131138.CrossRefGoogle ScholarPubMed
Grimaldi, G Jr, David, JR and and McMahon-Pratt, D (1987) Identification and distribution of New World Leishmania species characterized by serodeme analysis using monoclonal antibodies. American Journal of Tropical Medicine and Hygiene 36, 270287.CrossRefGoogle ScholarPubMed
Handman, E, Hocking, RE, Mitchell, GF and Spithill, TW (1983) Isolation and characterization of infective and non-infective clones of Leishmania tropica. Molecular and Biochemical Parasitology 7, 111126.CrossRefGoogle ScholarPubMed
Inbar, E, Akopyants, NS, Charmoy, M, Romano, A, Lawyer, P, Elnaiem, DEA, Kauffmann, F, Barhoumi, M, Grigg, M, Owens, K, Fay, M, Dobson, DE, Shaik, J, Beverley, SM and Sacks, D (2013) The mating competence of geographically diverse Leishmania major strains in their natural and unnatural sand fly vectors. PLoS Genetics 9, e1003672.CrossRefGoogle ScholarPubMed
Ishikawa, EAY, Silveira, FT, Magalhães, ALP, Guerra, RB Jr, Melo, MN, Gomes, R, Silveira, TGV and Shaw, JJ (2002) Genetic variation in populations of Leishmania species in Brazil. Transactions of the Royal Society of Tropical Medicine and Hygiene 96, 111121.CrossRefGoogle ScholarPubMed
Jiménez, M, Alvar, J and Tibayrenc, M (1997) Leishmania infantum is clonal in AIDS patients too: epidemiological implications. AIDS 11, 569572.CrossRefGoogle ScholarPubMed
Kamau, SW, Nunez, R and Grimm, F (2001) Flow cytometry analysis of the effect of allopurinol and the dinitroaniline compound (Chloralin) on the viability and proliferation of Leishmania infantum promastigotes. BMC Pharmacology 1, 110.CrossRefGoogle ScholarPubMed
Kink, JA and Chang, KP (1988) N-Glycosylation as a biochemical basis for virulence in Leishmania mexicana amazonensis. Molecular and Biochemical Parasitology 27, 181190.CrossRefGoogle ScholarPubMed
Lainson, R (1983) The American leishmaniases: some observations on their ecology and epidemiology. Transactions of the Royal Society of Tropical Medicine and Hygiene 77, 569596.CrossRefGoogle ScholarPubMed
Lambertz, U, Silverman, JM, Nandan, D, McMaster, WR, Clos, J, Foster, LJ and Reiner, NE (2012) Secreted virulence factors and immune evasion in visceral leishmaniasis. Journal of Leukocyte Biology 91, 887899.CrossRefGoogle ScholarPubMed
Leprohon, P, Fernandez-Prada, C, Gazanion, E, Monte-Neto, R and Ouellette, M (2015) Drug resistance analysis by next generation sequencing in Leishmania. International Journal for Parasitology: Drugs and Drug Resistance 5, 2635.Google ScholarPubMed
Lessa, MM, Lessa, HA, Castro, TW, Oliveira, A, Scherifer, A, Machado, P and Carvalho, EM (2007) Mucosal leishmaniasis: epidemiological and clinical aspects. Brazilian Journal of Otorhinolaryngology 73, 843847.CrossRefGoogle Scholar
Liew, FY, Li, Y and Millott, S (1990) Tumour necrosis factor (TNF-alpha) in leishmaniasis. II. TNF-alpha-induced macrophage leishmanicidal activity is mediated by nitric oxide from L-arginine. Immunology 71, 556.Google ScholarPubMed
Martínez, JE, Valderrama, L, Gama, V, Leiby, DA and Saravia, NG (2000) Clonal diversity in the expression and stability of the metastatic capability of Leishmania guyanensis in the golden hamster. Journal of Parasitology 86, 792800.CrossRefGoogle ScholarPubMed
Messaritakis, I, Mazeris, A, Koutala, E and Antoniou, M (2010) Leishmania donovani sl: evaluation of the proliferation potential of promastigotes using CFSE staining and flow cytometry. Experimental Parasitology 125, 384388.CrossRefGoogle ScholarPubMed
Moreira, ES, Anacleto, C and Petrillo-Peixoto, ML (1998) Effect of glucantime on field and patient isolates of New World Leishmania: use of growth parameters of promastigotes to assess antimony susceptibility. Parasitology Research 84, 720726.Google ScholarPubMed
Oliveira, FS, Valete-Rosalino, CM, Pacheco, SJ, Costa, FAC, Schubach, AO and Pacheco, RS (2013) American tegumentary leishmaniasis caused by Leishmania (Viannia) braziliensis: assessment of parasite genetic variability at intra- and inter-patient levels. Parasites & Vectors 6, 18.CrossRefGoogle ScholarPubMed
Pacheco, RS, Grimaldi, G, Momen, H and Morel, CM (1990) Population heterogeneity among clones of New World Leishmania species. Parasitology 100, 393398.CrossRefGoogle ScholarPubMed
Padigel, UM, Alexander, J and Farrell, JP (2003) The role of interleukin-10 in susceptibility of BALB/c mice to infection with Leishmania mexicana and Leishmania amazonensis. The Journal of Immunology 171, 37053710.CrossRefGoogle ScholarPubMed
Pal, S, Mandal, A and Duttagupta, S (2001) Studies on stibanate resistant Leishmania donovani isolates of Indian origin. Indian Journal of Experimental Biology 39, 249254.Google ScholarPubMed
Patino, LH, Muñoz, M, Cruz-Saavedra, L, Muskus, C and Ramírez, JD (2020) Genomic diversification, structural plasticity, and hybridization in Leishmania (Viannia) braziliensis. Frontiers in Cellular and Infection Microbiology 10, 193.CrossRefGoogle ScholarPubMed
Pereira, LO, Sousa, CS, Ramos, HC, Torres-Santos, EC, Pinheiro, LS, Alves, MR, Cuervo, P, Romero, GAS, Boité, MC, Porrozzi, R and Cupolillo, E (2021) Insights from Leishmania (Viannia) guyanensis in vitro behavior and intercellular communication. Parasites & Vectors 14, 114.CrossRefGoogle ScholarPubMed
Pinto-da-Silva, LH, Camurate, M, Costa, KA, Oliveira, SM, da Cunha-e-Silva, NL and Saraiva, EM (2002) Leishmania (Viannia) braziliensis metacyclic promastigotes purified using Bauhinia purpurea lectin are complement resistant and highly infective for macrophages in vitro and hamsters in vivo. International Journal for Parasitology 32, 13711377.CrossRefGoogle ScholarPubMed
Pomares, C, Marty, P, Bañuls, AL, Lemichez, E, Pratlong, F, Faucher, B, Jeddi, F, Moore, S, Michel, G, Aluru, S, Piarroux, R and Hide, M (2016) Genetic diversity and population structure of Leishmania infantum from southeastern France: evaluation using multi-locus microsatellite typing. PLoS Neglected Tropical Diseases 10, e0004303.CrossRefGoogle ScholarPubMed
Queiroz, A, Sousa, R, Heine, C, Cardoso, M, Guimaraes, LH, Machado, PRL, Carvalho, EM, Riley, LW, Wilson, ME and Schriefer, A (2012) Association between an emerging disseminated form of Leishmaniasis and Leishmania (Viannia) Braziliensis strain polymorphisms. Journal of Clinical Microbiology 50, 40284034.CrossRefGoogle ScholarPubMed
Rodríguez-Vega, A, Losada-Barragán, M, Berbert, LR, Mesquita-Rodrigues, C, Bombaça, ACS, Menna-Barreto, R, Aquino, P, Carvalho, PC, Padrón, G, de Jesus, JB and Cuervo, P (2021) Quantitative analysis of proteins secreted by Leishmania (Viannia) braziliensis strains associated to distinct clinical manifestations of American tegumentary leishmaniasis. Journal of Proteomics 232, 104077.CrossRefGoogle ScholarPubMed
Salloum, T, Moussa, R, Rahy, R, Al Deek, J, Khalifeh, I, El Hajj, R, Hall, N, Hirt, RP and Tokajian, S (2020) Expanded genome-wide comparisons give novel insights into population structure and genetic heterogeneity of Leishmania tropica complex. PLoS Neglected Tropical Diseases 14, e0008684.CrossRefGoogle ScholarPubMed
Schriefer, A, Schriefer, ALF, Goes-Neto, A, Guimarães, LH, Carvalho, LP, Almeida, RP and Carvalho, EM (2004) Multiclonal Leishmania braziliensis population structure and its clinical implication in a region of endemicity for American tegumentary leishmaniasis. Infection and Immunity 72, 508514.CrossRefGoogle Scholar
Silverman, JM, Clos, J, Horakova, E, Wang, AY, Wiesgigl, M, Kelly, I, Lynn, MA, MacMaster, WR, Foster, LJ, Levings, MK and Reiner, NE (2010) Leishmania exosomes modulate innate and adaptive immune responses through effects on monocytes and dendritic cells. The Journal of Immunology 185, 50115022.CrossRefGoogle ScholarPubMed
Tibayrenc, M and Ayala, FJ (2021) Leishmania and the model of predominant clonal evolution. Microorganisms 9, 2409.CrossRefGoogle ScholarPubMed
Tibayrenc, M, Kjellberg, F and Ayala, FJ (1990) A clonal theory of parasitic protozoa: the population structures of Entamoeba, Giardia, Leishmania, Naegleria, Plasmodium, Trichomonas, and Trypanosoma and their medical and taxonomical consequences. Proceedings of the National Academy of Sciences 87, 24142418.CrossRefGoogle ScholarPubMed
Viana, AG, Magalhães, LMD, Giunchetti, RC, Dutra, WO and Gollob, KJ (2018) Infection of human monocytes with Leishmania infantum strains induces a downmodulated response when compared with infection with Leishmania braziliensis. Frontiers in Immunology 8, 1896.CrossRefGoogle ScholarPubMed
Ward, AI, Olmo, F, Atherton, RL, Taylor, MC and Kelly, JM (2020) Trypanosoma cruzi amastigotes that persist in the colon during chronic stage murine infections have a reduced replication rate. Open Biology 10, 200261.CrossRefGoogle ScholarPubMed
Zabala-Peñafiel, A, Dias-Lopes, G, Cysne-Finkelstein, L, Conceição-Silva, F, Miranda, LDFC, Fagundes, A, Schubach, AO, Pimentel, MIF, Souza-Silva, F, Machado, LA and Alves, CR (2021) Serine proteases profiles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony. Scientific Reports 11, 111.CrossRefGoogle ScholarPubMed
Supplementary material: Image

de Albuquerque-Melo et al. supplementary material

Figure S1

Download de Albuquerque-Melo et al. supplementary material(Image)
Image 2.1 MB
Supplementary material: Image

de Albuquerque-Melo et al. supplementary material

Figure S2

Download de Albuquerque-Melo et al. supplementary material(Image)
Image 176.8 KB
Supplementary material: Image

de Albuquerque-Melo et al. supplementary material

Figure S3

Download de Albuquerque-Melo et al. supplementary material(Image)
Image 164.3 KB