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Flagella facilitate escape of Salmonella from oncotic macrophages.

ABSTRACT: The intracellular parasite Salmonella enterica serovar Typhimurium causes a typhoid-like systemic disease in mice. Whereas the survival of Salmonella in phagocytes is well understood, little has been documented about the exit of intracellular Salmonella from host cells. Here we report that in a population of infected macrophages Salmonella induces "oncosis," an irreversible progression to eukaryotic cell death characterized by swelling of the entire cell body. Oncotic macrophages (OnMphis) are terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling negative and lack actin filaments (F-actin). The plasma membrane of OnMphis filled with bacilli remains impermeable, and intracellular Salmonella bacilli move vigorously using flagella. Eventually, intracellular Salmonella bacilli intermittently exit host cells in a flagellum-dependent manner. These results suggest that induction of macrophage oncosis and intracellular accumulation of flagellated bacilli constitute a strategy whereby Salmonella escapes from host macrophages.

SUBMITTER: Sano G

PROVIDER: S-EPMC2168665 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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Flagella facilitate escape of Salmonella from oncotic macrophages.

Sano Gen-ichiro G Takada Yasunari Y Goto Shinichi S Goto Shinichi S Maruyama Kenta K Shindo Yutaka Y Oka Kotaro K Matsui Hidenori H Matsuo Koichi K

Journal of bacteriology 20070914 22

The intracellular parasite Salmonella enterica serovar Typhimurium causes a typhoid-like systemic disease in mice. Whereas the survival of Salmonella in phagocytes is well understood, little has been documented about the exit of intracellular Salmonella from host cells. Here we report that in a population of infected macrophages Salmonella induces "oncosis," an irreversible progression to eukaryotic cell death characterized by swelling of the entire cell body. Oncotic macrophages (OnMphis) are t ...[more]

PMID: 17873035

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Project description:BACKGROUND:Conflicting data have reported beneficial effects of crystalloids, hyper-oncotic albumin (20%ALB), and iso-oncotic albumin (5%ALB) in critically ill patients. Although hyper-oncotic albumin may minimize lung injury, recent studies have shown that human albumin may lead to kidney damage proportional to albumin concentration. In this context, we compared the effects of Ringer's lactate (RL), 20%ALB, and 5%ALB, all titrated according to similar hemodynamic goals, on pulmonary function, lung and kidney histology, and molecular biology in experimental acute lung injury (ALI). METHODS:Male Wistar rats received Escherichia coli lipopolysaccharide intratracheally (n?=?24) to induce ALI. After 24?h, animals were anesthetized and randomly assigned to receive RL, 20%ALB, or 5%ALB (n?=?6/group) to maintain hemodynamic stability (distensibility index of inferior vena cava <?25%, mean arterial pressure?>?65?mmHg). Rats were then mechanically ventilated for 6?h. Six animals, which received neither ventilation nor fluids (NV), were used for molecular biology analyses. RESULTS:The total fluid volume infused was higher in RL compared to 5%ALB and 20%ALB (median [interquartile range], 10.8[8.2-33.2] vs. 4.8[3.6-7.7] and 4.3[3.9-6.6] mL, respectively; p?=?0.02 and p?=?0.003). B-line counts on lung ultrasound (p?<?0.0001 and p?=?0.0002) and serum lactate levels (p?=?0.01 and p?=?0.01) were higher in RL than 5%ALB and 20%ALB. Diffuse alveolar damage score was lower in 5%ALB (10.5[8.5-12]) and 20%ALB (10.5[8.5-14]) than RL (16.5[12.5-20.5]) (p?<?0.05 and p?=?0.03, respectively), while acute kidney injury score was lower in 5%ALB (9.5[6.5-10]) than 20%ALB (18[15-28.5], p?=?0.0006) and RL (16 [15-19], p?=?0.04). In lung tissue, mRNA expression of interleukin (IL)-6 was higher in RL (59.1[10.4-129.3]) than in 5%ALB (27.0[7.8-49.7], p?=?0.04) or 20%ALB (3.7[7.8-49.7], p?=?0.03), and IL-6 protein levels were higher in RL than 5%ALB and 20%ALB (p =?0.026 and p =?0.021, respectively). In kidney tissue, mRNA expression and protein levels of kidney injury molecule (KIM)-1 were lower in 5%ALB than RL and 20%ALB, while nephronectin expression increased (p?=?0.01 and p?=?0.01), respectively. CONCLUSIONS:In a rat model of ALI, both iso-oncotic and hyper-oncotic albumin solutions were associated with less lung injury compared to Ringer's lactate. However, hyper-oncotic albumin resulted in greater kidney damage than iso-oncotic albumin. This experimental study is a step towards future clinical designs.

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Flagella facilitate escape of Salmonella from oncotic macrophages.

Publications

Flagella facilitate escape of Salmonella from oncotic macrophages.

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