Transcriptional and apoptotic responses of THP-1 cells to challenge with toxigenic, and non-toxigenic <it>Bacillus anthracis</it>
<p>Abstract</p> <p>Background</p> <p><it>Bacillus anthracis </it>secretes several virulence factors targeting different host organs and cell types during inhalational anthrax infection. The bacterial expression of a key virulence factor, lethal toxin (LeTx)...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2008-11-01
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| Series: | BMC Immunology |
| Online Access: | http://www.biomedcentral.com/1471-2172/9/67 |
| _version_ | 1818566841729024000 |
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| author | Bailey Charles Popova Anna Popova Taissia Liu Derong Schlauch Karen Zong Qin Chung Myung-Chul Bradburne Christopher Soppet Dan Popov Serguei |
| author_facet | Bailey Charles Popova Anna Popova Taissia Liu Derong Schlauch Karen Zong Qin Chung Myung-Chul Bradburne Christopher Soppet Dan Popov Serguei |
| author_sort | Bailey Charles |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p><it>Bacillus anthracis </it>secretes several virulence factors targeting different host organs and cell types during inhalational anthrax infection. The bacterial expression of a key virulence factor, lethal toxin (LeTx) is closely tied to another factor, edema toxin (EdTx). Both are transcribed on the same virulence plasmid (pXO1) and both have been the subject of much individual study. Their combined effect during virulent anthrax likely modulates both the global transcriptional and the phenotypic response of macrophages and phagocytes. In fact, responses brought about by the toxins may be different than each of their individual effects.</p> <p>Results</p> <p>Here we report the transcriptional and apoptotic responses of the macrophage-like phagocytic cell line THP-1 exposed to <it>B. anthracis </it>Sterne (pXO1<sup>+</sup>) spores, and <it>B. anthracis </it>Δ Sterne (pXO1<sup>-</sup>) spores. These cells are resistant to LeTx-induced cytolysis, a phenotype seen in macrophages from several mouse strains which are sensitive to toxigenic anthrax infection. Our results indicate that the pXO1-containing strain induces higher pro-inflammatory transcriptional responses during the first 4 hours of interaction with bacterium, evident in the upregulation of several genes relevant to Nf-κB, phosphatases, prostaglandins, and TNF-α, along with decreases in expression levels of genes for mitochondrial components. Both bacterial strains induce apoptosis, but in the toxigenic strain-challenged cells, apoptosis is delayed.</p> <p>Conclusion</p> <p>This delay in apoptosis occurs despite the much higher level of TNF-α secretion induced by the toxigenic-strain challenge. Interestingly, CFLAR, an important apoptotic inhibitor which blocks apoptosis induced by large amounts of extracellular TNF-α, is upregulated significantly during toxigenic-strain infection, but not at all during non-toxigenic-strain infection, indicating that it may play a role in blocking or delaying TNF-α-mediated apoptosis. The suppression of apoptosis by the toxigenic anthrax strain is consistent with the notion that apoptosis itself may represent a protective host cell response.</p> |
| first_indexed | 2024-12-14T01:58:47Z |
| format | Article |
| id | doaj.art-d8766d70abb845719246ecbaa0ff83d8 |
| institution | Directory Open Access Journal |
| issn | 1471-2172 |
| language | English |
| last_indexed | 2024-12-14T01:58:47Z |
| publishDate | 2008-11-01 |
| publisher | BMC |
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| series | BMC Immunology |
| spelling | doaj.art-d8766d70abb845719246ecbaa0ff83d82022-12-21T23:21:05ZengBMCBMC Immunology1471-21722008-11-01916710.1186/1471-2172-9-67Transcriptional and apoptotic responses of THP-1 cells to challenge with toxigenic, and non-toxigenic <it>Bacillus anthracis</it>Bailey CharlesPopova AnnaPopova TaissiaLiu DerongSchlauch KarenZong QinChung Myung-ChulBradburne ChristopherSoppet DanPopov Serguei<p>Abstract</p> <p>Background</p> <p><it>Bacillus anthracis </it>secretes several virulence factors targeting different host organs and cell types during inhalational anthrax infection. The bacterial expression of a key virulence factor, lethal toxin (LeTx) is closely tied to another factor, edema toxin (EdTx). Both are transcribed on the same virulence plasmid (pXO1) and both have been the subject of much individual study. Their combined effect during virulent anthrax likely modulates both the global transcriptional and the phenotypic response of macrophages and phagocytes. In fact, responses brought about by the toxins may be different than each of their individual effects.</p> <p>Results</p> <p>Here we report the transcriptional and apoptotic responses of the macrophage-like phagocytic cell line THP-1 exposed to <it>B. anthracis </it>Sterne (pXO1<sup>+</sup>) spores, and <it>B. anthracis </it>Δ Sterne (pXO1<sup>-</sup>) spores. These cells are resistant to LeTx-induced cytolysis, a phenotype seen in macrophages from several mouse strains which are sensitive to toxigenic anthrax infection. Our results indicate that the pXO1-containing strain induces higher pro-inflammatory transcriptional responses during the first 4 hours of interaction with bacterium, evident in the upregulation of several genes relevant to Nf-κB, phosphatases, prostaglandins, and TNF-α, along with decreases in expression levels of genes for mitochondrial components. Both bacterial strains induce apoptosis, but in the toxigenic strain-challenged cells, apoptosis is delayed.</p> <p>Conclusion</p> <p>This delay in apoptosis occurs despite the much higher level of TNF-α secretion induced by the toxigenic-strain challenge. Interestingly, CFLAR, an important apoptotic inhibitor which blocks apoptosis induced by large amounts of extracellular TNF-α, is upregulated significantly during toxigenic-strain infection, but not at all during non-toxigenic-strain infection, indicating that it may play a role in blocking or delaying TNF-α-mediated apoptosis. The suppression of apoptosis by the toxigenic anthrax strain is consistent with the notion that apoptosis itself may represent a protective host cell response.</p>http://www.biomedcentral.com/1471-2172/9/67 |
| spellingShingle | Bailey Charles Popova Anna Popova Taissia Liu Derong Schlauch Karen Zong Qin Chung Myung-Chul Bradburne Christopher Soppet Dan Popov Serguei Transcriptional and apoptotic responses of THP-1 cells to challenge with toxigenic, and non-toxigenic <it>Bacillus anthracis</it> BMC Immunology |
| title | Transcriptional and apoptotic responses of THP-1 cells to challenge with toxigenic, and non-toxigenic <it>Bacillus anthracis</it> |
| title_full | Transcriptional and apoptotic responses of THP-1 cells to challenge with toxigenic, and non-toxigenic <it>Bacillus anthracis</it> |
| title_fullStr | Transcriptional and apoptotic responses of THP-1 cells to challenge with toxigenic, and non-toxigenic <it>Bacillus anthracis</it> |
| title_full_unstemmed | Transcriptional and apoptotic responses of THP-1 cells to challenge with toxigenic, and non-toxigenic <it>Bacillus anthracis</it> |
| title_short | Transcriptional and apoptotic responses of THP-1 cells to challenge with toxigenic, and non-toxigenic <it>Bacillus anthracis</it> |
| title_sort | transcriptional and apoptotic responses of thp 1 cells to challenge with toxigenic and non toxigenic it bacillus anthracis it |
| url | http://www.biomedcentral.com/1471-2172/9/67 |
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