Comparison of invasion of fibroblasts and macrophages by high- and low-virulence Leptospira strains: colonization of the
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ORIGINAL PAPER
Comparison of invasion of Wbroblasts and macrophages by high- and low-virulence Leptospira strains: colonization of the host-cell nucleus and induction of necrosis by the virulent strain Liwei Li · David M. Ojcius · Jie Yan
Received: 6 March 2007 / Revised: 23 May 2007 / Accepted: 21 June 2007 / Published online: 11 July 2007 © Springer-Verlag 2007
Abstract The infection cycle of low- and high-virulence strains of Leptospira interrogans was compared in Wbroblasts 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. biXexa 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 Wbroblasts 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 Wbroblasts. However, the high-virulence strain could invade the host-cell nucleus, while the low-virulence strain remained in phagosomes. The L. biXexa 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 Wbroblasts, while the lowvirulence 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-inXammatory necrosis in Wbroblasts.
Communicated by Sebastian Suerbaum. L. Li · J. Yan (&) Department of Medical Microbiology and Parasitology, Medical School of Zhejiang University, Hangzhou, 310058, China e-mail: [email protected] D. M. Ojcius School of Natural Sciences, University of California, P.O. Box 2039, Merced, CA 95344, USA
Keywords Leptospira · Fibroblast · Macrophage · Invasion · Virulence · Nucleus
Introduction Leptospirosis spreads from animal urine to humans, the infection of which is characterized by hemorrhage, diarrhea, jaundice, severe renal impairment, and aseptic meningitis, and it is considered to be the most widespread anthropozoonosis in the world (Levett 2001; Meslin 1997; Lomar et al. 2000). The disease is common in farmers and veterinarians, and it can also be transmitted through contaminated water in Xooded areas. In particular, leptospirosis is one of the most important infectious diseases contracted in waterlogging areas and rice paddies (Sehgal et al. 2002; Barcellos and Sabroza 2001; Fuortes and Nettleman 1994). Leptospira is divided into two major groups, Leptospira interrogans sensu lato and L. biXexa sensu lato. The former is pathogenic for humans and animals, while the latter is free-living. More than 230 diVerent serovars belonging to 28 serogroups of L. interrogans have so far been identiWed, b
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