Naslov
Anti-Apoptotic Signalling in F. tularensis Infections

Autori
Šantić, Marina ; Jones, Snake ; Asare, Rexford ; Dorić, Miljenko ; Abu Kwaik, Yousef

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
ASM 107th General Meeting

Mjesto i datum
Toronto, Kanada, 21.05.2007. - 25.05.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
NF-kappa B; apoptosis; mutants

Sažetak
Francisella tularensis has been shown to induce apoptosis within murine and human macrophages. Several pathogens have been shown to promote or interfere with apoptosis through the inhibition or activation of nuclear transcription factor B (NF-κ B). The mechanisms and significance of F. tularensis-associated apoptosis through NF-κ B are not well understood. It is also not known the role of F. tularensis proteins, IglC and IglD, in induction of apoptosis and NF-κ B pathways. To examine nuclear translocation of the p65 subunit and apoptosis in F. tularensis-infected cells, monolayers of human monocytes derived macrophages (hMDMs) were infected with wt F. tularensis subsp. novicida, iglD or iglC and proceed for confocal microscopy analyses. To examine the effect of caffeic acid phenethyl ester (CAPE) on F. tularensis-induced nuclear translocation of the p65 subunit, hMDMs were treated with CAPE for 30 min prior to infection. At 30min, 1, 6, 24 and 48 h after infection, 83%, 96%, 44%, 43% and 35% of the wt of F. tularensis-infected macrophages, respectively, showed nuclear translocation of the p65 subunit. At 30 min after infection, 80% of the iglD and 50% of the iglC mutant-infected macrophages exhibited nuclear translocation of the p65 subunit. However, by 6 h and 24 h after infection, only 18% of the iglD and 9% of the iglC mutant-infected macrophages showed nuclear translocation of the p65 subunit, similar to uninfected cells. Our data also showed that nuclear translocation of the p65 subunit was detected in only ~15% of iglD, iglC or wt F. tularensis-infected macrophages in the presence of CAPE. TUNEL labeling for apoptotic nuclei revealed in CAPE-treated cells, 30%, 15%, 10% and 25% of uninfected, iglD, iglC-infected and wt-infected cells, respectively, were apoptotic. We conclude that the mechanism of sustained nuclear translocation of the p65 subunit in F. tularensis infection is mediated by IglC and IglD at the later stage of infection. Our data show that the activation of NF-κ B plays a role in protecting the infected cells from external apoptotic stimuli to maintain viability of the infected cells.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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