IFN-gamma-induced apoptosis and microbicidal activity in monocytes harboring the intracellular bacterium Coxiella burnetii require membrane TNF and homotypic cell adherence - PubMed (original) (raw)

IFN-gamma-induced apoptosis and microbicidal activity in monocytes harboring the intracellular bacterium Coxiella burnetii require membrane TNF and homotypic cell adherence

Jérôme Dellacasagrande et al. J Immunol. 2002.

Abstract

IFN-gamma is critical for the protection against intracellular bacteria through activation of the antimicrobial machinery of phagocytes. Coxiella burnetii, the etiological agent of Q fever, is a strictly intracellular bacterium that inhabits monocytes/macrophages. We previously showed that IFN-gamma induced C. burnetii killing by promoting the apoptosis of infected monocytes. We show in this study that IFN-gamma-induced apoptosis of infected monocytes was characterized by a time- and dose-dependent activation of caspase-3. IFN-gamma-mediated caspase-3 activation and C. burnetii killing depend on the expression of membrane TNF. Indeed, TNF was transiently expressed on the cell surface of infected monocytes a few hours after IFN-gamma treatment. In addition, anti-TNF Abs inhibited IFN-gamma-mediated caspase-3 activation whereas soluble TNF had no effect on infected cells. Concomitantly, IFN-gamma induced homotypic adherence of C. burnetii-infected monocytes. The latter required the interaction of beta(2) integrins with CD54. When adherence was disrupted by pipetting, by a combination of Abs specific for CD11b, CD18, and CD54, or by an antisense oligonucleotide targeting CD18 mRNA, both cell apoptosis and bacterial killing induced by IFN-gamma were inhibited. Thus, adherence via CD54/beta(2) integrins together with membrane TNF are required to eliminate C. burnetii-infected cells through cell contact-dependent apoptosis. Our results reveal a new component of the antimicrobial arsenal mobilized by IFN-gamma against infection by intracellular bacteria.

PubMed Disclaimer

Cited by

Coxiella burnetii inhibits apoptosis in human THP-1 cells and monkey primary alveolar macrophages.
Voth DE, Howe D, Heinzen RA. Voth DE, et al. Infect Immun. 2007 Sep;75(9):4263-71. doi: 10.1128/IAI.00594-07. Epub 2007 Jul 2. Infect Immun. 2007. PMID: 17606599 Free PMC article.
Sustained activation of Akt and Erk1/2 is required for Coxiella burnetii antiapoptotic activity.
Voth DE, Heinzen RA. Voth DE, et al. Infect Immun. 2009 Jan;77(1):205-13. doi: 10.1128/IAI.01124-08. Epub 2008 Nov 3. Infect Immun. 2009. PMID: 18981248 Free PMC article.
Acquired STAT4 deficiency as a consequence of cancer chemotherapy.
Lupov IP, Voiles L, Han L, Schwartz A, De La Rosa M, Oza K, Pelloso D, Sahu RP, Travers JB, Robertson MJ, Chang HC. Lupov IP, et al. Blood. 2011 Dec 1;118(23):6097-106. doi: 10.1182/blood-2011-03-341867. Epub 2011 Oct 13. Blood. 2011. PMID: 21998209 Free PMC article.
Activation of IFN-γ/STAT/IRF-1 in hepatic responses to Klebsiella pneumoniae infection.
Lin YC, Lu MC, Lin C, Chiang MK, Jan MS, Tang HL, Liu HC, Lin WL, Huang CY, Chen CM, Lai YC. Lin YC, et al. PLoS One. 2013 Nov 6;8(11):e79961. doi: 10.1371/journal.pone.0079961. eCollection 2013. PLoS One. 2013. PMID: 24223208 Free PMC article.
T cells are essential for bacterial clearance, and gamma interferon, tumor necrosis factor alpha, and B cells are crucial for disease development in Coxiella burnetii infection in mice.
Andoh M, Zhang G, Russell-Lodrigue KE, Shive HR, Weeks BR, Samuel JE. Andoh M, et al. Infect Immun. 2007 Jul;75(7):3245-55. doi: 10.1128/IAI.01767-06. Epub 2007 Apr 16. Infect Immun. 2007. PMID: 17438029 Free PMC article.

IFN-gamma-induced apoptosis and microbicidal activity in monocytes harboring the intracellular bacterium Coxiella burnetii require membrane TNF and homotypic cell adherence - PubMed (original) (raw)