Kif1C, a kinesin-like motor protein, mediates mouse macrophage resistance to anthrax lethal factor

Watters, James; Dewar, Ken; Lehoczky, Jessica A.; Boyartchuk, Victor L.; Dietrich, William F.

doi:10.1016/s0960-9822(01)00476-6

Cited by 87 publications

(72 citation statements)

References 27 publications

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“…This implies that resistance is not due to defects in vesicular acidification (5). As mentioned earlier, the proteolysis of MKKs is comparable in sensitive and resistant cells (16,17). Thus, resistance is due to a defect at a stage occurring after proteolysis.…”

Section: Anthrax Infections Are Initiated By Endospores Ofmentioning

confidence: 59%

“…The toxic activity of LF depends on its protease activity (4), suggesting that proteolysis of one or more cellular protein(s) unleashes a cascade of events resulting in the death of the intoxicated macrophages. Indeed, cleavage of several mitogen-activated protein kinase (MAPK) kinases (MKKs) has been observed (15)(16)(17). However, the physiological importance of MKK proteolysis relative to macrophage cytolysis cannot be established because similar cleavage is observed in macrophages that are resistant to LeTx (16,17).…”

Section: Anthrax Infections Are Initiated By Endospores Ofmentioning

confidence: 99%

“…It is clear that proper function of kif1C is required for LeTx resistance, but how this protein is involved in LeTx-elicited changes in macrophages is unknown (17). The kif1C protein has been excluded as a target of LF-mediated proteolysis (17).…”

Section: Anthrax Infections Are Initiated By Endospores Ofmentioning

confidence: 99%

“…Injection of LeTx into CBA/J mice, whose macrophages are sensitive to LeTx, results in a more rapid death compared with A/J mice, whose macrophages are resistant to LeTx-induced cytolysis (5). However, the sensitivity of macrophages to LeTx in vitro does not correlate with in vivo susceptibility to infection of either encapsulated or non-encapsulated strains of B. anthracis (5,16,17). Because macrophages can be activated by encounters with infected bacteria (19,20), we addressed whether macrophage activation has an effect on cell viability in LeTx-treated LeTx-resistant macrophages.…”

Section: Anthrax Infections Are Initiated By Endospores Ofmentioning

confidence: 99%

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Sensitizing Anthrax Lethal Toxin-resistant Macrophages to Lethal Toxin-induced Killing by Tumor Necrosis Factor-α

Kim

Jing

Hoebe

et al. 2003

Journal of Biological Chemistry

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Macrophages from different inbred mouse strains exhibit striking differences in their sensitivity to anthrax lethal toxin (LeTx)-induced cytolysis. Although LeTxinduced cytolysis of macrophages plays an important role in the outcome of anthrax infection, the sensitivity of macrophages in vitro does not correlate with in vivo susceptibility to infection of Bacillus anthracis. This divergence suggests that additional factors other than LeTx are involved in the cytolysis of LeTx-resistant macrophages in vivo. We found that LeTx-resistant macrophages became sensitive to LeTx-induced cytolysis when these cells were activated by bacterial components. Tumor necrosis factor-␣ induced by bacterial components was a key factor that cooperated with LeTx in inducing LeTx-resistant macrophage death. Tumor necrosis factor-␣/LeTx-induced death of LeTx-resistant macrophages was dependent on mTor (mammalian target of rapamycin), but independent of caspases. Our data indicate that host responses to anthrax infection contribute to cytolysis of LeTx-resistant macrophages.

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Section: Anthrax Infections Are Initiated By Endospores Ofmentioning

confidence: 59%

Section: Anthrax Infections Are Initiated By Endospores Ofmentioning

confidence: 99%

Section: Anthrax Infections Are Initiated By Endospores Ofmentioning

confidence: 99%

Section: Anthrax Infections Are Initiated By Endospores Ofmentioning

confidence: 99%

See 2 more Smart Citations

Sensitizing Anthrax Lethal Toxin-resistant Macrophages to Lethal Toxin-induced Killing by Tumor Necrosis Factor-α

Kim

Jing

Hoebe

et al. 2003

Journal of Biological Chemistry

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“…21,22 The BXD strains were used recently to study variation in the pathogenicity of bovine spongiform encephalopathy and to uncover genes modulating anthrax and pox lethality. [23][24][25] Among the different panels of RI strains, we selected the BXD set produced from an intercross of C57BL/6J and DBA/2J. The parental strains are known to differ in response to many pathogens.…”

Section: Introductionmentioning

confidence: 99%

Susceptibility to severe streptococcal sepsis: use of a large set of isogenic mouse lines to study genetic and environmental factors

et al. 2007

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Variation in responses to pathogens is influenced by exposure history, environment and the host's genetic status. We recently demonstrated that human leukocyte antigen class II allelic differences are a major determinant of the severity of invasive group A streptococcal (GAS) sepsis in humans. While in-depth controlled molecular studies on populations of genetically wellcharacterized humans are not feasible, it is now possible to exploit genetically diverse panels of recombinant inbred BXD mice to define genetic and environmental risk factors. Our goal in this study was to standardize the model and identify genetic and nongenetic covariates influencing invasive infection outcomes. Despite having common ancestors, the various BXD strains (n strains ¼ 33, n individuals ¼ 445) showed marked differences in survival. Mice from all strains developed bacteremia but exhibited considerable differences in disease severity, bacterial dissemination and mortality rates. Bacteremia and survival showed the expected negative correlation. Among nongenetic factors, age -but not sex or weight -was a significant predictor of survival (P ¼ 0.0005). To minimize nongenetic variability, we limited further analyses to mice aged 40-120 days and calculated a corrected relative survival index that reflects the number of days an animal survived post-infection normalized to all significant covariates. Genetic background (strain) was the most significant factor determining susceptibility (Pp0.0001), thus underscoring the strong effect of host genetic variation in determining susceptibility to severe GAS sepsis. This model offers powerful unbiased forward genetics to map specific quantitative trait loci and networks of pathways modulating the severity of GAS sepsis.

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Neurologic Complications of Anthrax

Meyer

2003

Arch Neurol

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A review of the literature suggests that the major neurologic symptom complex of infection by Bacillus anthracis is a fulminant and rapidly fatal hemorrhagic meningoencephalitis and that the reported initial mode of entry can be via the cutaneous or inhalation route. For febrile patients with acute neurologic deterioration with associated findings of dark necrotic pustules on the extremities, gram-positive rods in the cerebrospinal fluid, and multifocal areas of unexplained intracerebral hemorrhage on computed tomographic scans, anthrax should be considered within the differential diagnosis. A low cerebrospinal fluid glucose level has been reported, with gram-positive rods often noted on the gram stain of the cerebrospinal fluid in severely affected patients. Reports indicate that death usually occurs within a week.

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Kif1C, a kinesin-like motor protein, mediates mouse macrophage resistance to anthrax lethal factor

Cited by 87 publications

References 27 publications

Sensitizing Anthrax Lethal Toxin-resistant Macrophages to Lethal Toxin-induced Killing by Tumor Necrosis Factor-α

Sensitizing Anthrax Lethal Toxin-resistant Macrophages to Lethal Toxin-induced Killing by Tumor Necrosis Factor-α

Susceptibility to severe streptococcal sepsis: use of a large set of isogenic mouse lines to study genetic and environmental factors

Neurologic Complications of Anthrax

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