engleski

F. tularensis Induces Apoptosis in the Lungs of BALB/c mice via a Mechanism That Requires IglC

Francisella tularensis is a highly virulent facultative intracellular bacterium and is considered a potential biological warfare agent. F. tularensis subsp. novicida is attenuated in humans but it causes tularemia in mice that is similar to that caused by subsp. tularensis. Although it has been shown that F. tularensis induces apoptosis in murine macrophages the mechanisms of F. tularensis-associated apoptosis are not well understood. In addition, nothing is known about the in vivo mechanism of apoptosis and the role of IglD protein in pathogenesis of the disease. BALB/c mice were intravenously inoculated with 104 cfu of F. tularensis subsp. novicida or the iglD mutant. At different time points after infection (2, 24, 48, 72 hours, 5 and 7 days) mice were sacrificed, the lungs were removed and proceed for immunohistology. Sections were cut and stained for TUNEL followed by staining for Francisella polyclonal Abs. The apoptosis into the lungs of mice in response to F. tularensis infection were assessed by confocal microscopy. We showed that F. tularensis replicated in the lungs of BALB/c mice with the peak of infection at 48h, while the iglD mutant did not replicate at all. At 2 and 24h after infection of BALB/c mice with F. tularensis most of the cells had normal morphology without any sign of apoptosis. However, at 48 hours after infection of BALB/c mice with F. tularensis most of the cells became apoptotic. In the lungs of BALB/c mice infected with the iglD mutant histopathological changes were insignificant without any apoptotic process. F. tularenis induces apoptosis in the lungs of BALB/c mice. Apoptosis is triggered at late stages of infection, concomitant with termination of intracellular replication. IglD protein plays an important role in induction of apoptosis and pathogenesis of tularemia as well.

cell death; Francisella; hMDS; mice

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