Rapid Pathogen-Induced Apoptosis: A Mechanism Used by Dendritic Cells to Limit Intracellular Replication of <italic>Legionella pneumophila</italic> Export

@article{citeulike:5014788, abstract = {<title>Author Summary</title> <p>The immune system is designed to identify microbes that enter the body and elicit responses that prevent the replication and dissemination of these organisms. Dendritic cells play an important role in regulating host immunity to pathogens. Their phagocytic capacity enables DCs to internalize and destroy most microbes, and the ability of DCs to migrate to specialized lymphoid organs is important for inducing antigen-specific immunity. Here, we analyzed interactions between DCs and <italic>Legionella pneumophila</italic>, a bacterial pathogen that can subvert phagocytic host cell functions to create a vacuole that permits intracellular replication. We found that <italic>L. pneumophila</italic> infection rapidly induced DCs to commit cell death through apoptosis. Rapid apoptosis was not observed after infection of macrophages, which are the phagocytic cells that support <italic>L. pneumophila</italic> replication in the lungs of infected animals. Using cells derived from knockout mice, we found that DCs deficient in the proteins Bax and Bak, which are essential for induction of the apoptosis pathway, were unable to restrict the intracellular replication of <italic>L. pneumophila</italic>. Likewise, overproduction of Bcl-2, which is a negative regulator of apoptosis, resulted in DCs that were permissive for <italic>L. pneumophila</italic> replication. These data indicate DCs have the ability to rapidly undergo apoptosis when infected with a microbe capable of replicating intracellularly, and this response effectively prevents pathogen replication. We hypothesize that this response may be designed to interfere with the migration of infected DCs through the lymphatic system, which would prevent DCs from serving as a ” Trojan Horse” that transports pathogenic microbes from peripheral sites to central organs.</p>}, author = {Nogueira, Catarina V. and Lindsten, Tullia and Jamieson, Amanda M. and Case, Christopher L. and Shin, Sunny and Thompson, Craig B. and Roy, Craig R.}, citeulike-article-id = {5014788}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.ppat.1000478}, day = {12}, doi = {10.1371/journal.ppat.1000478}, journal = {PLoS Pathog}, keywords = {pathogenesis}, month = {June}, number = {6}, pages = {e1000478+}, posted-at = {2009-06-29 20:01:42}, priority = {2}, publisher = {Public Library of Science}, title = {Rapid Pathogen-Induced Apoptosis: A Mechanism Used by Dendritic Cells to Limit Intracellular Replication of <italic>Legionella pneumophila</italic>}, url = {http://dx.doi.org/10.1371/journal.ppat.1000478}, volume = {5}, year = {2009} }

TY - JOUR ID - citeulike:5014788 L3 - citeulike-article-id:5014788 N2 - <title>Author Summary</title> <p>The immune system is designed to identify microbes that enter the body and elicit responses that prevent the replication and dissemination of these organisms. Dendritic cells play an important role in regulating host immunity to pathogens. Their phagocytic capacity enables DCs to internalize and destroy most microbes, and the ability of DCs to migrate to specialized lymphoid organs is important for inducing antigen-specific immunity. Here, we analyzed interactions between DCs and <italic>Legionella pneumophila</italic>, a bacterial pathogen that can subvert phagocytic host cell functions to create a vacuole that permits intracellular replication. We found that <italic>L. pneumophila</italic> infection rapidly induced DCs to commit cell death through apoptosis. Rapid apoptosis was not observed after infection of macrophages, which are the phagocytic cells that support <italic>L. pneumophila</italic> replication in the lungs of infected animals. Using cells derived from knockout mice, we found that DCs deficient in the proteins Bax and Bak, which are essential for induction of the apoptosis pathway, were unable to restrict the intracellular replication of <italic>L. pneumophila</italic>. Likewise, overproduction of Bcl-2, which is a negative regulator of apoptosis, resulted in DCs that were permissive for <italic>L. pneumophila</italic> replication. These data indicate DCs have the ability to rapidly undergo apoptosis when infected with a microbe capable of replicating intracellularly, and this response effectively prevents pathogen replication. We hypothesize that this response may be designed to interfere with the migration of infected DCs through the lymphatic system, which would prevent DCs from serving as a “Trojan Horse” that transports pathogenic microbes from peripheral sites to central organs.</p> IS - 6 JF - PLoS Pathog TI - Rapid Pathogen-Induced Apoptosis: A Mechanism Used by Dendritic Cells to Limit Intracellular Replication of <italic>Legionella pneumophila</italic> PB - Public Library of Science VL - 5 SP - e1000478 KW - pathogenesis AU - Nogueira, Catarina AU - Lindsten, Tullia AU - Jamieson, Amanda AU - Case, Christopher AU - Shin, Sunny AU - Thompson, Craig AU - Roy, Craig PY - 2009/06/12/ UR - http://dx.doi.org/10.1371/journal.ppat.1000478 ER -