Coxiella burnetii Induces Apoptosis during Early Stage Infection via a Caspase-Independent Pathway in Human Monocytic THP-1 Cells

Zhang, Y., et al. (2012). PLoS ONE 7(1): e30841

Speaker: Yu-ping Hong (洪羽屏)            )                         Time: 15:00~16:00, Dec. 26, 2012

Commentator: Dr. Lien-I Hor (何漣漪 博士)  )        Place: Room 601

Abstract:

Coxiella burnetii is an obligate intracellular bacterium that causes acute or chronic Q fever infection, leading to febrile illness, atypical pneumonia or endocarditic disease [1]. Many obligate intracellular bacterial pathogens modulate host cell apoptosis to facilitate their intracellular survival and dissemination [2]. Therefore, the ability of Coxiella burnetii to modulate cell apoptosis may also be critical in disease development. The major target cells of Coxiella burnetii are the  monocyte/macrophage. In this study, the authors use the human monocytic THP-1 cell to determine howCoxiella burnetii NMII is involved in host cell apoptosis. In the early stage of infection, typical apoptotic cell morphology and DNA fragments were detected. In addition, FACS analysis using Annexin-V-PI double staining also indicated that NMII infected cells underwent apoptosis. They also examined the activities of Caspase-3 and its substrate PARP to identify the signaling pathway. Interestingly, the results showed that Caspase-3 was not activated, while its target molecule PARP was activated. These data suggest that NMII induces apoptosis through a caspase-independent pathway. Western blotting analysis showed that NMII infection induced caspase-independent apoptosis through a mechanism involving cytochrome C release, cytosol-tmitochondrial translocation of Bax and nuclear translocation of AIF in THP-1 cells. NMII infection increased TNF-α production, suggesting that TNF-α may play a role in the upstream signaling involved in NMII induced apoptosis. Neutralization of TNF-α and inhibition of replication of Coxiella burnetii both blocked PARP activation, suggesting they are involved in NMII infection-triggered apoptosis during an early stage of infection. In summary, the authors proposed that Coxiella burnetii induces apopotosis through a caspase-independent pathway.

Reference:

1.      Maurin M, Raoult D (1999) Q fever. Clin Microbiol Rev 12: 518–553.

2.      Gao LY, Kwaik YA (2000) The modulation of host cell apoptosis by intracellular bacterial pathogens. Trends Microbiol 8: 306–313.