Naslov
Induction of Apoptosis During Intracellular replication of Legionella pneumophila in the Lungs of Mice

Autori
Šantić, Marina ; Molmeret, Maelle ; Jones, Snake ; Asare, Rexford ; Abu-Zant, Alaeddin ; Dorić, Miljenko ; Abu Kwaik, Yousef

Vrsta, podvrsta i kategorija rada
Radovi u zbornicima skupova, cjeloviti rad (in extenso), znanstveni

Izvornik
6th International Conference on Legionella. Book / Cianciotto, Nick - Chicago (IL) : ASM, 2006, 35-36

Skup
6th International Conference on Legionella

Mjesto i datum
Chicago (IL), Sjedinjene Američke Države, 16.10.2005. - 20.10.2005

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Apoptosis; Mice; Dot/Icm

Sažetak
Background: Legionella pneumophila has been shown to induce apoptosis within macrophages, monocytic cell lines and alveolar epithelial cells. It has been shown that L. pneumophila induces Dot/Icm-depended activation of caspase-3 in the host cell that results in apoptosis. The induction of caspase-3 activation apoptosis by L. pneumophila is very well documented in vitro. It is not known whether it occurs in vivo during Legionnaires’ disease. It is also not known whether genetically susceptible inbred mice strains but not resistant ones are susceptible to the L. pneumophila Dot/Icm-mediated induction of apoptosis. Methods: A/J and BALB/c mice, were intratracheally inoculated with 106 cfu of L. pneumophila AA100 or dotA mutant. At different time points after infection (2, 24, 48 and 72 hours) mice were sacrificed, the lungs were removed and proceed for immunohistology. Sections were cut and stained for TUNEL followed by staining for Legionella mAbs. The apoptosis into the lungs of mice in response to L. pneumophila infection were assessed by confocal microscopy. Results: We showed that L. pneumophila AA100 replicated in the lungs of A/J mice with the peak of infection at 48h, while the dotA mutant did not replicate at all. L. pneumophilla AA100 did not replicate in the lungs of BALB/c mice. At 2h after infection of A/J mice with L. pneumophilla AA100 most of the cells had normal morphology without any sign of apoptosis. However, at 24 and 48 hours after infection of A/J mice with L. pneumophilla AA100 most of the cells became apoptotic. L. pneumophilla replicated intracellulary and was mainly localized in apoptotic cells. In the lungs of A/J mice infected with the dotA mutant histopathological changes were insignificant without any apoptotic process. We did not observed any apoptotic process in the lungs of BALB/c mice infected with L. pneumophilla AA100. Conclusions: L. pneumophilla AA100 induces apoptosis in vivo during late stages of Legionnaires' disease in experimental animals. Genetically susceptible A/J mice are susceptible to the L. pneumophilla Dot/Icm-mediated induction of apoptosis. Apoptosis is triggered at late stages of infection, concomitant with termination of intracellular replication. BALB/c mice are resistant to infection of L. pneumophilla AA100, as well as induction of apoptosis.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA