Abstract
Acinetobacter baumannii outer membrane protein A (AbOmpA) is a potential virulence factor that induces epithelial cell death, but its pathologic effects on the immune system have yet to be determined. The present study investigated the pathologic events occurring in dendritic cells (DCs) exposed to a cytotoxic concentration of AbOmpA. AbOmpA induced early-onset apoptosis and delayed-onset necrosis in DCs. AbOmpA targeted the mitochondria and induced the production of reactive oxygen species (ROS). ROS were directly responsible for both apoptosis and necrosis of AbOmpA-treated DCs. These results demonstrate that the AbOmpA secreted from A. baumannii induces DC death, which may impair T cell biology to induce adaptive immune responses against A. baumannii.
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References
Banchereau, J., F. Briere, C. Caux, J. Davoust, S. Lebecque, Y.J. Liu, B. Pulendran, and K. Palucka. 2000. Immunobiology of dendritic cells. Annu. Rev. Immunol. 18, 767–811.
Choi, C.H., S.H. Hyun, J.Y. Lee, J.S. Lee, Y.S. Lee, S.A. Kim, J.P. Chae, S.M. Yoo, and J.C. Lee. 2008a. Acinetobacter baumannii outer membrane protein A targets the nucleus and induces cytotoxicity. Cell. Microbiol. 10, 309–319.
Choi, C.H., E.Y. Lee, Y.C. Lee, T.I. Park, H.J. Kim, S.H. Hyun, S.A. Kim, S.K. Lee, and J.C. Lee. 2005. Outer membrane protein 38 of Acinetobacter baumannii localizes to the mitochondria and induces apoptosis of epithelial cells. Cell. Microbiol. 7, 1127–1138.
Choi, C.H., J.S. Lee, Y.C. Lee, T.I. Park, and J.C. Lee. 2008b. Acinetobacter baumannii invades epithelial cells and outer membrane protein A mediates interactions with epithelial cells. BMC Microbiol. 8, 216.
Crompton, M. 2003. On the involvement of mitochondrial intermembrane junctional complexes in apoptosis. Curr. Med. Chem. 10, 1473–1484.
De Trez, C., B. Pajak, M. Brait, N. Glaichenhaus, J. Urbain, M. Moser, G. Lauvau, and E. Muraille. 2005. TLR4 and Toll-IL-1 receptor domain-containing adapter-inducing IFN-β, but not MyD88, regulate Escherichia coli-induced dendritic cell maturation and apoptosis in vivo. J. Immunol. 175, 839–846.
Dijkshoorn, L., A. Nemec, and H. Seifert. 2007. An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii. Nat. Rev. Microbiol. 5, 939–951.
Galmiche, A., J. Rassow, A. Doye, S. Cagnol, J.C. Chambard, S. Contamin, V. de Thillot, and et al. 2000. The N-terminal 34 kDa fragment of Helicobacter pylori vacuolating cytotoxin targets mitochondria and induces cytochrome c release. EMBO J. 19, 6361–6370.
Jyothisri, K., V. Deepak, and M.R. Rajeswari. 1999. Purification and characterization of a major 40 kDa outer membrane protein of Acinetobacter baumannii. FEBS Lett. 443, 57–60.
Kim, S.W., C.H. Choi, D.C. Moon, J.S. Jin, J.H. Lee, J.H. Shin, J.M Kim, and et al. 2009. Serum resistance of Acinetobacter baumannii through the binding of factor H to outer membrane proteins. FEMS Microbiol. Lett. 301, 224–231.
Kim, D.W., H. Chu, D.H. Joo, M.S. Jang, J.H. Choi, S.M. Park, Y.J. Choi, S.H. Han, and C.H. Yun. 2008. OspF directly attenuates the activity of extracellular signal-regulated kinase during invasion by Shigella flexneri in human dendritic cells. Mol. Immunol. 45, 3295–3301.
Kwon, S.O., Y.S. Gho, J.C. Lee, and S.I. Kim. 2009. Proteome analysis of outer membrane vesicles from a clinical Acinetobacter baumannii isolate. FEMS Microbiol. Lett. 297, 150–156.
Lee, H.W., Y.M. Koh, J. Kim, J.C. Lee, Y.C. Lee, S.Y. Seol, D.T. Cho, and J. Kim. 2008. Capacity of multidrug-resistant clinical isolates of Acinetobacter baumannii to form biofilm and adhere to epithelial cell surfaces. Clin. Microbiol. Infect. 14, 49–54.
Lee, J.S., J.C. Lee, C.M. Lee, I.D. Jung, Y.I. Jeong, E.Y. Seong, H.Y. Chung, and Y.M. Park. 2007. Outer membrane protein A of Acinetobacter baumannii induces differentiation of CD4+ T cells toward a Th1 polarizing phenotype through the activation of dendritic cells. Biochem. Pharmacol. 74, 86–97.
Müller, A., D. Günther, V. Brinkmann, R. Hurwitz, T.F. Meyer, and T. Rudel. 2000. Targeting of the pro-apoptotic VDAC-like porin (PorB) of Neisseria gonorrhoeae to mitochondria of infected cells. EMBO J. 19, 5332–5343.
Nougayrède, J.P. and M.S. Donnenberg. 2004. Enteropathogenic Escherichia coli EspF is targeted to mitochondria and is required to initiate the mitochondrial death pathway. Cell. Microbiol. 6, 1097–1111.
Pistor, S., T. Chakraborty, K. Niebuhr, E. Domann, and J. Wehland. 1994. The ActA protein of Listeria monocytogenes acts as a nucleator inducing reorganization of the actin cytoskeleton. EMBO J. 13, 758–763.
Ricci, J.E., N. Waterhouse, and D.R. Green. 2003. Mitochondrial functions during cell death, a complex (I–V) dilemma. Cell Death Differ. 10, 488–492.
Richter, C., V. Gogvadze, R. Laffranchi, R. Schlapbach, M. Schweizer, M. Suter, P. Walter, and M. Yaffee. 1995. Oxidants in mitochondria: from physiology to diseases. Biochim. Biophys. Acta 1271, 67–74.
Skulachev, V.P. 2006. Bioenergetic aspects of apoptosis, necrosis and mitopsis. Apoptosis 11, 473–485.
Worgall, S., K. Martushova, A. Busch, L. Lande, and R.G. Crystal. 2002. Apoptosis induced by Pseudomonas aeruginosa in antigen presenting cells is diminished by genetic modification with CD40 ligand. Pediatr. Res. 52, 636–644.
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Lee, J.S., Choi, C.H., Kim, J.W. et al. Acinetobacter baumannii outer membrane protein a induces dendritic cell death through mitochondrial targeting. J Microbiol. 48, 387–392 (2010). https://doi.org/10.1007/s12275-010-0155-1
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DOI: https://doi.org/10.1007/s12275-010-0155-1