| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité Universitätsmedizin Berlin, Berlin;
Institute of Biochemistry Charité, Berlin; and
Robert Koch-Institut, Research Group NG5 Pathogenesis of Legionella Infections, Berlin, Germany
In mice, different alleles of the mNAIP5 (murine neuronal apoptosis inhibitory protein-5)/mBirc1e gene determine whether macrophages restrict or support intracellular replication of Legionella pneumophila, and whether a mouse is resistant or (moderately) susceptible to Legionella infection. In the resistant mice strains, the nucleotide-binding oligomerization domain (Nod)-like receptor (NLR) family member mNAIP5/mBirc1e, as well as the NLR protein mIpaf (murine ICE protease-activating factor), are involved in recognition of Legionella flagellin and in restriction of bacterial replication. Human macrophages and lung epithelial cells support L. pneumophila growth, and humans can develop severe pneumonia (Legionnaires disease) after Legionella infection. The role of human orthologs to mNAIP5/mBirc1e and mIpaf in this bacterial infection has not been elucidated. Herein we demonstrate that flagellin-deficient L. pneumophila replicate more efficiently in human THP-1 macrophages, primary monocyte-derived macrophages, and alveolar macrophages, and in A549 lung epithelial cells compared with wild-type bacteria. Additionally, we note expression of the mNAIP5 ortholog hNAIP in all cell types examined, and expression of hIpaf in human macrophages. Gene silencing of hNAIP or hIpaf in macrophages or of hNAIP in lung epithelial cells leads to an enhanced bacterial growth, and overexpression of both molecules strongly reduces Legionella replication. In contrast to experiments with wild-type L. pneumophila, hNAIP or hIpaf knock-down affects the (enhanced) replication of flagellin-deficient Legionella only marginally. In conclusion, hNAIP and hIpaf mediate innate intracellular defense against flagellated Legionella in human cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by grants given by the Deutsche Forschungsgemeinschaft, the Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin, and the Jürgen Manchot Stiftung (to B.O.), and by the Bundesministerium für Bildung und Forschung-funded network PROGRESS (to S.H. and N.S.). Parts of this work will be included in the M.D. thesis of M.V.
2 Address correspondence and reprint requests to Dr. Bastian Opitz, Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail address: bastian.opitz{at}charite.de
3 Abbreviations used in this paper: LCV, Legionella-containing vacuole; ASC, apoptosis-associated speck-like protein containing a CARD; CARD, caspase recruitment domain; COX, cyclooxygenase; FAK, focal adhesion kinase; Ipaf, ICE protease-activating factor; LDH, lactate dehydrogenase; MOI, multiplicity of infection; NAIP, neuronal apoptosis inhibitory protein; NLR, Nod-like receptor; Nod, nucleotide-binding oligomerization domain; PRR, pattern recognition receptor; RLR, RIG-like receptors; RT, room temperature.
This article has been cited by other articles:
|
|
 |
|
  K. Vardarova, S. Scharf, F. Lang, B. Schmeck, B. Opitz, J. Eitel, A. C. Hocke, H. Slevogt, A. Flieger, S. Hippenstiel, et al. PKC{alpha} and PKC{epsilon} differentially regulate Legionella pneumophila-induced GM-CSF Eur. Respir. J., November 1, 2009; 34(5): 1171 - 1179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Fortier, K. Doiron, M. Saleh, S. Grinstein, and P. Gros Restriction of Legionella pneumophila Replication in Macrophages Requires Concerted Action of the Transcriptional Regulators Irf1 and Irf8 and Nod-Like Receptors Naip5 and Nlrc4 Infect. Immun., November 1, 2009; 77(11): 4794 - 4805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Rumble and C. S. Duckett Diverse functions within the IAP family J. Cell Sci., November 1, 2008; 121(21): 3505 - 3507. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
