Abstract
Background Legionella pneumophila is an intracellular bacterial pathogen that invades and replicates within alveolar macrophages through injection of ∼300 effector proteins by its Dot/Icm type IV translocation apparatus. The bona fide F-box protein, AnkB, is a nutritional virulence effector that triggers macrophages to generate a surplus of amino acids, which is essential for intravacuolar proliferation. Therefore, the ankB mutant represents a novel genetic tool to determine the transcriptional response of human monocyte-derived macrophages (hMDMs) to actively replicating L. pneumophila.Methodology/Principal FindingsHere, we utilized total human gene microarrays to determine the global transcriptional response of hMDMs to infection by wild type or the ankB mutant of L. pneumophila. The transcriptomes of hMDMs infected with either actively proliferating wild type or non-replicative ankB mutant bacteria were remarkably similar. The transcriptome of infected hMDMs was predominated by up-regulation of inflammatory pathways (IL-10 anti-inflammatory, interferon signaling and amphoterin signaling), anti-apoptosis, and down-regulation of protein synthesis pathways. In addition, L. pneumophila modulated diverse metabolic pathways, particularly those associated with bio-active lipid metabolism, and SLC amino acid transporters expression.Conclusion/SignificanceTaken together, the hMDM transcriptional response to L. pneumophila is independent of intra-vacuolar replication of the bacteria and primarily involves modulation of the immune response and metabolic as well as nutritional pathways.
Highlights
Legionella pneumophila is found ubiquitously in the aquatic environment and shares an intimate intracellular relationship with many species of amoeba and ciliates [1, 2, 3]
Global transcriptional response of human monocyte-derived macrophages (hMDMs) to infection by wild type and an ankB mutant of L. pneumophila
We utilized the ankB mutant, that resides within an ER-derived Legionella-containing vacuolar (LCV), similar to the wild type strain [15], as a genetic tool to determine if the transcriptional response of hMDMs to infection by L. pneumophila was dependent on intravacuolar proliferation
Summary
Legionella pneumophila is found ubiquitously in the aquatic environment and shares an intimate intracellular relationship with many species of amoeba and ciliates [1, 2, 3]. Methodology/Principal Findings: Here, we utilized total human gene microarrays to determine the global transcriptional response of hMDMs to infection by wild type or the ankB mutant of L. pneumophila.
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