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Trojan Horse Effect: Phagocyte-Mediated Streptococcus iniae Infection of Fish

Department of Clinical Microbiology, The Hebrew University—Hadassah Medical School, Jerusalem 91120,¹ Department of Poultry and Fish Diseases, The Kimron Veterinary Institute, Bet Dagan 50250,³ Dan Fish Farms, Kibbutz Dan, Upper Galilee 12245, Israel,⁴ Unité de Virologie et Immunologie Moleculaires, Institut National de la Recherche Agronomique, Jouy en Josas 78352, France,² Department of Fish Pathology, IZS—State Veterinary Institute, 06126 Perugia, Italy⁵

Received 28 May 2002/ Returned for modification 3 August 2002/ Accepted 3 February 2003

The salmonid macrophage-like cell line RTS-11 and purified trout pronephros phagocytes were used to analyze in vitro entry and survival of two Streptococcus iniae serotypes. Efficient invasion by S. iniae occurred in both cells, but only the type II strain persisted in pronephros phagocytes for at least 48 h. Ex vivo models of opsonin-dependent phagocytosis by pronephros phagocytes demonstrated increased phagocytosis efficacy. Analysis of phagocytes collected from diseased fish demonstrated that 70% of the bacteria contained in the blood during the septic phase of the disease were located within phagocytes, suggesting an in vivo intracellular lifestyle. In addition to the augmented levels of bacteremia and enhanced survival within phagocytes, S. iniae type II induces considerable apoptosis of phagocytes. These variabilities in intramacrophage lifestyle might explain differences in the outcomes of infections caused by different serotypes. The generalized septic disease associated with serotype II strains is linked not only to the ability to enter and multiply within macrophages but also to the ability to cause considerable death of macrophages via apoptotic processes, leading to a highly virulent infection. We assume that the phenomenon of survival within phagocytes coupled to their apoptosis plays a crucial role in S. iniae infection. In addition, it may provide the pathogen an efficient mechanism of translocation into the central nervous system.

Editor: V. J. DiRita

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