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

Abstract

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 ϳ70% 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.

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“…Another possibility is that the bacteria simply use the phagosome as a safe haven where they are protected from host immune responses and exposure to antimicrobials without replicating. Zlotkin et al (2003) reported a similar phenomenon in salmonid phagocytes exposed to S. iniae. Dubbed the 'Trojan horse effect', these investigators demonstrated that phagocytized S. iniae not only survive in fish macrophages, but induce apoptosis of these cells, effectively minimizing the host immune response while being transported and delivered to typically inaccessible regions such as the central nervous system.…”

New Insights into the Evolution of IFNs: Zebrafish Group II IFNs Induce a Rapid and Transient Expression of IFN-Dependent Genes and Display Powerful Antiviral Activities

“…In fact, zfIFN1 is able to rapidly induce the expression of NOS2b, which might contribute to the killing of S. iniae by macrophages by means of the production of reactive nitrogen and oxygen intermediates. The involvement of fish macrophages in the elimination of S. iniae is thought to be essential because the capsule of this bacterium impairs phagocytic clearance and contributes to virulence (22), and the bacterium is able to multiply within macrophages and has the ability to kill macrophages via the induction of apoptotic processes (19).…”

“…The virus stock was propagated in EPC cells and titrated in 96-well plates according to Reed and Muench (18). The strain KFP 404 (serotype II) of Streptococcus iniae was provided by Dr. A. Eldar (The Hebrew University-Hadassah Medical School, Jerusalem, Israel) and cultured in brain/heart infusion broth as described previously (19). Ten adult zebrafish were challenged at 26°C in 10-liter tanks i.p.…”

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“…The virus stock was propagated in EPC cells and titrated in 96-well plates according to the report of Reed and Muench (32). The strain KFP 404 (serotype II) of S. iniae was kindly provided by Dr. A. Eldar and cultured in brain-heart infusion broth as described previously (33). Ten adult zebrafish were challenged at 26°C in 10-liter tanks by i.p.…”