Skip to main content
SpringerLink
Log in

Comparison of invasion of fibroblasts and macrophages by high- and low-virulence Leptospira strains: colonization of the host-cell nucleus and induction of necrosis by the virulent strain

  • Original Paper
  • Published:
Archives of Microbiology Aims and scope Submit manuscript

Abstract

The infection cycle of low- and high-virulence strains of Leptospira interrogans was compared in fibroblasts and macrophages. L. interrogans serovar Lai strain Lai was used as a representative high-virulence strain, while L. interrogans serovars Pomona strain Luo was used as a low-virulence strain. L. biflexa serovar Patoc strain Patoc I, a nonparasitic strain of Leptospira, was used as a control. Both the high- and low-virulence strains could adhere to fibroblasts and macrophages using one or both ends of the spirochete, which was followed by phagocytosis of both strains. Both strains adhered more strongly to macrophages than fibroblasts. However, the high-virulence strain could invade the host-cell nucleus, while the low-virulence strain remained in phagosomes. The L. biflexa strain neither adhered to nor invaded either cell type. Both of the L. interrogans strains also induced cell death (mostly necrosis) of macrophages, whether or not the spirochetes were viable, suggesting that leptospiral virulence is unrelated to macrophage death. However, the high-virulence strain induced mainly necrosis in fibroblasts, while the low-virulence strain induced more apoptosis. Thus, the main feature distinguishing the two L. interrogans strains is the ability of the high-virulence strain to invade the host-cell nucleus and induce pro-inflammatory necrosis in fibroblasts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Baldwin TJ, Knutton S, Haigh R, Williams PH, Palmer HM, Aitken A, Borriello SP (1996) Hijacking host cell signal transduction mechanisms during infection with enteropathogenic Escherichia coli. Biochem Soc Trans 24:552–558

    PubMed  CAS  Google Scholar 

  • Barcellos C, Sabroza PC (2001) The place behind the case: leptospirosis risks and associated environmental conditions in a flood-related outbreak in Rio de Janeiro. Cad Saude Publica 17:59–67

    PubMed  Google Scholar 

  • Barocchi MA, Ko AI, Reis MG, McDonald KL, Riley LW (2002) Rapid translocation of polarized MDCK cell monolayers by Leptospira interrogans, an invasive but nonintracellular pathogen. Infect Immun 70:6926–6932

    Article  PubMed  CAS  Google Scholar 

  • Boullier S, Tasca C, Milon A (2003) New flow cytometric method to quantify the inhibition of enteropathogenic Escherichia coli adhesion by anti-adhesin antibodies. Cytometry 53:79–87

    Article  PubMed  CAS  Google Scholar 

  • Brito TD, Menezes LF, Lima DM, Lourenco S, Silva AM, Alves VA (2006) Immunohistochemical and in situ hybridization studies of the liver and kidney in human leptospirosis. Virchows Arch 448:576–583

    Article  PubMed  CAS  Google Scholar 

  • Brumell JH, Grinstein S (2003) Role of lipid-mediated signal transduction in bacterial internalization. Cell Microbiol 5:287–297

    Article  PubMed  CAS  Google Scholar 

  • Clark MA, Hirst BH, Jepson MA (1998) Inoculum composition and Salmonella Pathogenicity island I regulated M cell and epithelial destruction by Salmonella typhimurium. Infect Immun 66:727–731

    Google Scholar 

  • Contributu LS (1970) Study of pulmonary localizations in Leptospirosis. Excerpta Med Int Med 24:393

    Google Scholar 

  • Dai B (1992) Advances in research on leptospira and human leptospirosis in China. Chin Med Sci J 7:239–243

    PubMed  CAS  Google Scholar 

  • Eichelberg K, Galán JE (1999) Differential regulation of Salmonella typhimurium type III secreted proteins by pathogenicity island 1-encoded transcriptional activators InvF and HilA. Infect Immun 67:4099–4105

    PubMed  CAS  Google Scholar 

  • Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM (1998) Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest 101:890–898

    PubMed  CAS  Google Scholar 

  • Faine S, Adler B, Bolin C, Perolat P (1999) Leptospira and leptospirosis. MediSci, Melbourne, pp 76–77

    Google Scholar 

  • Faine S, Shahar A, Aronson M (1964) Phagocytosis and its significance in leptospiral infection. Aust J Exp Biol Med Sci 42:579–588

    PubMed  CAS  Google Scholar 

  • Falkow S, Isberg RR, Portnoy DA (1992) The interaction of bacteria with mammalian cells. Annu Rev Cells Biol 8:333–363

    CAS  Google Scholar 

  • Frick IM, Schmidtchen A, Sjobring V (2003) Interaction between M proteins of Streptococcus pyogenes and glycosaminoglycans promote bacterial adhesion to host cells. Eur J Biochem 270:2303–2311

    Article  PubMed  CAS  Google Scholar 

  • Fuortes L, Nettleman M (1994) Leptospirosis: a consequence of the Iowa flood. Iowa Med 84:449–450

    PubMed  CAS  Google Scholar 

  • Gerard E, Guyot F, Philippot P, Lopez-Garcia P (2005) Fluorescence in situ hybridisation coupled to ultra small immunogold detection to identify prokaryotic cells using transmission and scanning electron microscopy. J Microbiol Methods 63:20–28

    Article  PubMed  CAS  Google Scholar 

  • Goebel W, Kuhn M (2000) Bacterial replication in the host cell cytosol. Curr Opin Microbiol 3:49–53

    Article  PubMed  CAS  Google Scholar 

  • Gouin E, Gantelet H, Egile C, Lasa I, Ohayon H, Villiers V, Gounon P, Sansonetti PJ, Cossart P (1999) A comparative study of the actin-based motilities of the pathogenic bacteria Listeria monocytogenes, Shigella flexneri and Rickettsia conorii. J Cell Sci 112:1697–1708

    PubMed  CAS  Google Scholar 

  • Jaradat ZW, Bhunia AK (2003) Adhesion, invasion and translocation characteristics of Listeria monocytogenes serotype in Caco-2 cell and mouse models. Appl Environ Microbiol 69:3640–3645

    Article  PubMed  CAS  Google Scholar 

  • Johnson RC, Faine S (1984) Genus I. Leptospira Noguchi 1917, 755. In: Krieg NR, Holt JG (eds) Bergey’s manual of systematic bacteriology, 1st edn, vol 1. Williams and Wilkins, Baltimore, pp 62–67

    Google Scholar 

  • Joiner KA, Ganz T, Albert J, Rotrosen D (1989) The opsonizing ligand on Salmonella typhimurium influences incorporation of specific, but not azurophil, granule constituents into neutrophil phagosomes. J Cell Biol 109:2771–2782

    Article  PubMed  CAS  Google Scholar 

  • Kallstrom H, Hansson PP, Jonsson AB (2000) Cholera toxin and extracllular Ca2+ induce adherence of non-piliated Neisseria: evidence for an important role of G-proteins and Rho in the bacteria-cell interaction. Cell Microbiol 2:341–351

    Article  PubMed  CAS  Google Scholar 

  • Lee SH, Kim KA, Park YG, Seong IW, Kim MJ, Lee YJ (2000) Identification and partial characterization of a novel hemolysin from Leptospira interrogans serovar Lai. Gene 254:19–28

    Article  PubMed  CAS  Google Scholar 

  • Levett PN (2001) Leptospirosis. Clin Microbiol Rev 14:296–326

    Article  PubMed  CAS  Google Scholar 

  • Lomar AV, Diament D, Torres JR (2000) Leptospirosis in Latin America. Infect Dis Clin North Am 14:23–39

    Article  PubMed  CAS  Google Scholar 

  • Menzies BE, Kourteva I (1998) Internalization of Staphylococcus aureus by endothelial cells induce apoptosis. Infect Immun 66:5994–5998

    PubMed  CAS  Google Scholar 

  • Menzie BE, Kourteva I (2000) Staphylococcus aureus alpha-toxin induces apoptosis in endothelial cell. FEMS Immunol Med Microbiol 29:39–45

    Google Scholar 

  • Merien F, Baranton G, Perolat P (1997) Invasion of Vero cells and Induction of apoptosis in marcrophage by pathogenic Leptospira interrogans are correlated with virulence. Infect Immun 65:729–738

    PubMed  CAS  Google Scholar 

  • Meslin FX (1997) Global aspects of emerging and potential zoonoses: a WHO perspective. Emerg Infect Dis 3:223–228

    Article  PubMed  CAS  Google Scholar 

  • Perfettini JL, Gissot M, Souque P, Ojcius DM (2002) Modulation of apoptosis during infection by Chlamydia. Methods Enzymol 358:334–344

    Article  PubMed  CAS  Google Scholar 

  • Saravanan R, Rajendran P, Thyagarajan SP, Smythe LD, Norris MA, Symonds ML, Dohnt MF (2000) Leptospira autumnalis isolated from a human case from Avadi, India, and the serovar’s predominance in local rat and bandicoot populations. Ann Trop Med Parasitol 94:503–506

    PubMed  CAS  Google Scholar 

  • Savill J, Fadok V (2000) Corpse clearance defines the meaning of cell death. Nature 407:784–788

    Article  PubMed  CAS  Google Scholar 

  • Sehgal SC, Sugunan AP, Vijayachari P (2002) Outbreak of leptospirosis after the cyclone in Orissa. Natl Med J India 15:22–23

    PubMed  CAS  Google Scholar 

  • Seijo A, Coto H, Juan JS, Videla J, Deodato B, Cernigoi B, Messina OG, Collia O, Bassadoni D de, Schtirbu R, Olenchuk A, Mazzonelli GD de, Parma A (2002) Lethal leptospiral pulmonary hemorrhage: an emerging disease in Buenos Aires, Argentina. Emerg Infect Dis 8:1004–1005

    PubMed  Google Scholar 

  • Sunbul M, Esen S, Leblebicioglu H, Hokelek M, Pekbay A, Eroglu C (2001) Rattus norvegicus acting as reservoir of leptospira interrogans in the Middle Black Sea region of Turkey, as evidenced by PCR and presence of serum antibodies to Leptospira strain. Scand J Infect Dis 33:896–898

    Article  PubMed  CAS  Google Scholar 

  • Thomas DD, Higbie LM (1990) In vitro association of leptospira with host cells. Infect Immun 58:581–585

    PubMed  CAS  Google Scholar 

  • Vihn T, Faine S, Adler B (1984) Adhesion of leptospira to mouse fibroblast (L929) and its enhancement by specific antibody. J Med Microbiol 18:73–85

    Article  Google Scholar 

  • Yang CW, Wu MS, Pan MJ, Hong JJ, Yu CC, Vandewalle A, Huang CC (2000) Leptospira outer membrane protein activates NF-kappaB and downstream genes expressed in medullary thick ascending limb cells. J Am Soc Nephrol 11:2017–2026

    PubMed  CAS  Google Scholar 

  • Yrlid U, Wick MJ (2000) Salmonella-induced apoptosis of infected macrophages results in presentation of a bacteria-encoded antigen after uptake by bystander dendritic cells. J Exp Med 191:613–624

    Article  PubMed  CAS  Google Scholar 

  • Zhang YX, Geng Y, Bi B, He JY, Wu CF, Guo XK, Zhao GP (2005) Identification and classification of all potential hemolysin encoding genes and their products from Leptospira interrogans serogroup Icterohae-morrhagiae serovar Lai. Acta Pharmacol Sin 26:453–461

    Article  PubMed  CAS  Google Scholar 

  • Zychlinsky A, Perdomo JJ, Sansonetti PJ (1994) Molecular and cellular mechanisms of tissue invasion by Shigella flexneri. Ann NY Acad Sci 730:197–208

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (30170049).

Author information

Authors and Affiliations

  1. Department of Medical Microbiology and Parasitology, Medical School of Zhejiang University, Hangzhou, 310058, China

    Liwei Li & Jie Yan

  2. School of Natural Sciences, University of California, P.O. Box 2039, Merced, CA, 95344, USA

    David M. Ojcius

Authors
  1. Liwei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David M. Ojcius
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jie Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jie Yan.

Additional information

Communicated by Sebastian Suerbaum.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, L., Ojcius, D.M. & Yan, J. Comparison of invasion of fibroblasts and macrophages by high- and low-virulence Leptospira strains: colonization of the host-cell nucleus and induction of necrosis by the virulent strain. Arch Microbiol 188, 591–598 (2007). https://doi.org/10.1007/s00203-007-0280-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00203-007-0280-3

Keywords

Search

Navigation