Depletion of lymphocytes, but not neutrophils, via apoptosis in a murine model of Vibrio vulnificus infection

Kashimoto, Takeshi; Ueno, Shunji; Hayashi, Hisae; Hanajima, Miyuki; Yoshioka, Kazuki; Yoshida, Kenji; Mutoh, Ken-ichiro; Susa, Nobuyuki

doi:10.1099/jmm.0.45861-0

Cited by 20 publications

(17 citation statements)

References 24 publications

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“…Blood taken from patients with chronic liver disease showed decreased neutrophil activity compared to the blood of healthy individuals, and survival of V. vulnificus in human blood is inversely correlated with phagocytosis by neutrophils (44). Based on these data and a study showing increased neutrophil concentrations in the peritoneal cavity upon infection with V. vulnificus, the response of neutrophils to V. vulnificus has been implicated as a disease determinant for this organism (44,56,144,154). One of these studies, however, did use unencapsulated strains (the significance of which is discussed later in this review), thus diminishing the potential role neutrophils play in controlling V. vulnificus infection (44,154).…”

Section: Host Resistancementioning

confidence: 99%

“…In addition to neutrophils, macrophages have also been suggested to play a part in defense against V. vulnificus. During infection, this bacterium reduces the number of lymphocytes through apoptotic activity, but neutrophil numbers do not decrease, indicating that other leukocytes are being targeted (56). Specific examination of macrophages revealed that clinical strains of V. vulnificus were able to induce macrophage apoptosis (57).…”

Section: Host Resistancementioning

confidence: 99%

“…These receptors are commonly found on the surfaces of immune and epithelial cells, and some are specifically involved in recognizing antigens produced by gram-negative bacteria (28,101). Studies examining the activation of Toll-like receptor 4 (TLR4) showed that it does not appear to participate in lymphocyte apoptosis upon exposure to V. vulnificus and is therefore unlikely to participate in the immune response during infection (56). However, TLR2 was shown to be activated by a surface lipoprotein (encoded by ilpA) of V. vulnificus, and its activation resulted in the production of TNF-␣ and IL-6, which have been established as associated with V. vulnificus infection (33).…”

Section: Host Resistancementioning

confidence: 99%

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Vibrio vulnificus: Disease and Pathogenesis

2009

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Vibrio vulnificus is an opportunistic human pathogen that is highly lethal and is responsible for the overwhelming majority of reported seafood-related deaths in the United States (30,117). This bacterium is a part of the natural flora of coastal marine environments worldwide and has been isolated from water, sediments, and a variety of seafood, including shrimp, fish, oysters, and clams (4,7,25,26,43,97,109,116,118,149,165). Consumption of seafood (primarily raw oysters) containing V. vulnificus can result in a severe, fulminant systemic infection. Characteristics of this disease include fever, chills, nausea, hypotensive septic shock, and the formation of secondary lesions on the extremities of patients (11,22,41,74,115,146). This primary septicemia is the most lethal infection caused by V. vulnificus, with an average mortality rate exceeding 50% (30, 41). A review of 459 U.S. cases reported by the FDA between 1992 and 2007 (J. D. Oliver, unpublished) revealed that 51.6% of the patients died. Interestingly, 85.6% of the cases were male; this aspect of the infection is discussed later in this review. Of 180 cases in 2002 to 2007 for which FDA data were available, 92.8% of patients had consumed raw oysters prior to the onset of symptoms and 95.3% had some preexisting disease(s). The latter are clearly associated with V. vulnificus infection, with liver diseases, such as cirrhosis or hepatitis, being the most common (116). In addition to septicemia, V. vulnificus can produce serious wound infections that typically result from exposure of open wounds to water harboring the bacterium (114). Wound infections are frequently contracted as a result of recreational swimming, fishing injuries, or seafood handling (7, 46). Like systemic disease, wound infections progress rapidly to cellulitis, ecchymoses, and bullae, which can progress to necrotizing fasciitis at the site of infection; however, the mortality rate for wound infections (ca. 25%) is lower than that for systemic disease (10,13,74). This organism possesses a wide array of virulence factors, including acid neutralization, capsular polysaccharide expression, iron acquisition, cytotoxicity, motility, and expression of proteins involved in attachment and adhesion. These factors likely require concerted expression for pathogenesis to take place and appear to be under the control of global regulators. Overall, V. vulnificus is a complex microorganism with physiological characteristics that contribute to its survival in the marine environment and in the human host.

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Section: Host Resistancementioning

confidence: 99%

Section: Host Resistancementioning

confidence: 99%

Section: Host Resistancementioning

confidence: 99%

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Vibrio vulnificus: Disease and Pathogenesis

2009

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“…Recently, Kashimoto et al reported that lymphocytes but not neutrophils were depleted, via apoptosis, by V. vulnificus (12). Extensive loss of lymphocytes was observed in patients due to polymicrobial sepsis, and in a mouse model of sepsis, polycaspase and caspase 3 inhibitor prevented lymphocyte apoptosis and improved survival (9,10).…”

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confidence: 99%

Vibrio vulnificus Damages Macrophages during the Early Phase of Infection

et al. 2007

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Vibrio vulnificus is an estuarine bacterium that can cause primary septicemia as well as serious wound infections. Generally, clinical isolates have a high lethal effect compared with environmental isolates. However, little is known about the mechanisms by which V. vulnificus causes disease. In this study, we compared the pathogenicity of a clinical isolate, strain M2799, with that of an environmental isolate, strain JCM3731. The clinical isolate showed 100 times higher lethality in mice than the environmental isolate. In strain M2799-inoculated mice, the number of macrophages decreased significantly, whereas there was no appreciable change in the number of macrophages in strain JCM3731-inoculated mice. The clinical isolate showed high cytotoxic activity, especially to macrophages, compared with the environmental isolate in vitro. The growth of the clinical isolate was almost completely inhibited in the presence of macrophages. Moreover, the survival rate of the clinical isolate-inoculated mice increased by recruitment of macrophages. These results indicate that V. vulnificus infection progresses by damage to macrophages during the early phase of infection.Vibrio vulnificus is a gram-negative halophilic marine bacterium that is found in estuarine waters and contaminates oysters and other seafood. Consumption of raw contaminated seafood or contamination of wounds with V. vulnificus can lead to septicemia or wound infection, respectively. Infection with V. vulnificus is associated with predisposing conditions such as hepatitis, cirrhosis, diabetes, hemochromatosis, and immune compromise (1,2,15,22). V. vulnificus causes a rapid and severe disease process resulting in extensive tissue damage. Mortality was up to 50% in septic patients, with most of them dying within 48 h with a fulminate course after infection (8). In addition, clinical isolates have generally high lethality in mice and high cytotoxicity to various cultured cells compared with environmental isolates (11,26,27).Several putative virulence factors of V. vulnificus, such as metalloprotease (14, 19), hemolysin-cytolysin (7, 23), capsular polysaccharide (CPS) (25,32), and means of iron acquisition (e.g., siderophore) (18), have been reported in vivo and in vitro. Lethality in animal models is clearly related to CPS expression. Both CPS expression and virulence are associated with an opaque colony morphology (25, 33). V. vulnificus strains with encapsulated phenotypes (opaque colonies) have a much higher lethality in mice than those with unencapsulated phenotypes (translucent colonies). This is considered to be due to CPS providing a protective barrier against phagocytosis by neutrophils and macrophages and against bacteriolysis by complement (24, 29, 31, 32). Many reports have focused on the interaction between phagocytes and CPS (17,25,28,33); however, there is little in the literature on host immune responses to V. vulnificus. Despite considerable published research on the virulence factors of V. vulnificus, very little definitive information has been ...

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“…Isolated peripheral lymphocytes (1.0  10 6 cells/ml) suspended in RPMI-1640 medium were incubated with Dex or organotin compounds at 37C for 1 or 3 hr. After incubation, the lymphocytes were stained with FITCAnnexin V and propidium iodide (PI) using an Annexin-V-FLUOS Staining Kit (Roche Diagnostics GmbH, Penzberg, Analysis of DNA fragmentation: DNA fragmentation was analyzed as described previously with some modifications [14,27]. Briefly, thymus tissues from the mice were gently glass-ground to dissociate the cells, suspended in cold HBSS and then gently passed through a stainless steel mesh to obtain single-cell suspensions of thymocytes.…”

Section: Chemicalsmentioning

confidence: 99%

Reduction in Peripheral Lymphocytes and Thymus Atrophy Induced by Organotin Compounds In Vivo

et al. 2009

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ABSTRACT. To clarify the involvement of apoptosis in the immunotoxicity of organotin compounds, we examined the induction of apoptosis in the peripheral lymphocytes and thymus of mice treated with triphenyltin (TPT), tributyltin (TBT) or dexamethasone (Dex). Application of TPT or TBT and Dex resulted in a transient reduction in peripheral lymphocytes at 3 to 6 hr, and thymus atrophy was observed at 6 and 24 hr after administration. Lymphocyte subpopulation analysis showed that TPT and TBT induced a greater reduction in B cells than in T cells. The maximum levels of organotin in the blood were about 450 ng TPT/ml in the TPT-treated mice, and 170 ng TBT/ml in the TBT-treated mice. When the isolated peripheral lymphocytes were incubated with the organotins at 500 ng/ml, TPT and TBT induced necrosis in over 70% of cells, while both organotins caused lower percentages of apoptosis as well as necrosis after 3 hr at 100 ng/ml. In the thymus, although in vivo treatment of mice with Dex caused apoptosis, neither apoptotic nor necrotic thymocytes were observed in the TPT-and TBT-treated mice, indicating that the thymus atrophy might be caused by the antiproliferative effects of these organotin compounds. Thus, our results did not support the idea that apoptosis played a decisive part in the immunotoxicity of the organotin compounds in vivo.KEY WORDS: organotin compounds, peripheral lymphocytes, thymus atrophy.

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Depletion of lymphocytes, but not neutrophils, via apoptosis in a murine model of Vibrio vulnificus infection

Cited by 20 publications

References 24 publications

Vibrio vulnificus: Disease and Pathogenesis

Vibrio vulnificus: Disease and Pathogenesis

Vibrio vulnificus Damages Macrophages during the Early Phase of Infection

Reduction in Peripheral Lymphocytes and Thymus Atrophy Induced by Organotin Compounds In Vivo

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