Specific Remodeling of Splenic Architecture by Cytomegalovirus
Efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. Mouse cytomegalovirus (MCMV) infection induces significant remodeling of splenic microarchitecture, i...
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| Format: | Online |
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Public Library of Science
2006
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1386719/ |
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pubmed-13867192006-04-18 Specific Remodeling of Splenic Architecture by Cytomegalovirus Benedict, Chris A De Trez, Carl Schneider, Kirsten Ha, Sukwon Patterson, Ginelle Ware, Carl F Research Article Efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. Mouse cytomegalovirus (MCMV) infection induces significant remodeling of splenic microarchitecture, including loss of marginal zone macrophage populations and dissolution of T and B cell compartmentalization. MCMV preferentially infected the splenic stroma, targeting endothelial cells (EC) as revealed using MCMV-expressing green fluorescent protein. MCMV infection caused a specific, but transient transcriptional suppression of secondary lymphoid chemokine (CCL21). The loss of CCL21 was associated with the failure of T lymphocytes to locate within the T cell zone, although trafficking to the spleen was unaltered. Expression of CCL21 in lymphotoxin (LT)-α–deficient mice is dramatically reduced, however MCMV infection further reduced CCL21 levels, suggesting that viral modulation of CCL21 was independent of LTα signaling. Activation of LTβ-receptor signaling with an agonistic antibody partially restored CCL21 mRNA expression and redirected transferred T cells to the splenic T cell zone in MCMV-infected mice. These results indicate that virus-induced alterations in lymphoid tissues can occur through an LT-independent modulation of chemokine transcription, and targeting of the LT cytokine system can counteract lymphoid tissue remodeling by MCMV. Public Library of Science 2006-03 2006-03-03 /pmc/articles/PMC1386719/ /pubmed/16518465 http://dx.doi.org/10.1371/journal.ppat.0020016 Text en © 2006 Benedict et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Benedict, Chris A De Trez, Carl Schneider, Kirsten Ha, Sukwon Patterson, Ginelle Ware, Carl F |
| spellingShingle |
Benedict, Chris A De Trez, Carl Schneider, Kirsten Ha, Sukwon Patterson, Ginelle Ware, Carl F Specific Remodeling of Splenic Architecture by Cytomegalovirus |
| author_facet |
Benedict, Chris A De Trez, Carl Schneider, Kirsten Ha, Sukwon Patterson, Ginelle Ware, Carl F |
| author_sort |
Benedict, Chris A |
| title |
Specific Remodeling of Splenic Architecture by Cytomegalovirus |
| title_short |
Specific Remodeling of Splenic Architecture by Cytomegalovirus |
| title_full |
Specific Remodeling of Splenic Architecture by Cytomegalovirus |
| title_fullStr |
Specific Remodeling of Splenic Architecture by Cytomegalovirus |
| title_full_unstemmed |
Specific Remodeling of Splenic Architecture by Cytomegalovirus |
| title_sort |
specific remodeling of splenic architecture by cytomegalovirus |
| description |
Efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. Mouse cytomegalovirus (MCMV) infection induces significant remodeling of splenic microarchitecture, including loss of marginal zone macrophage populations and dissolution of T and B cell compartmentalization. MCMV preferentially infected the splenic stroma, targeting endothelial cells (EC) as revealed using MCMV-expressing green fluorescent protein. MCMV infection caused a specific, but transient transcriptional suppression of secondary lymphoid chemokine (CCL21). The loss of CCL21 was associated with the failure of T lymphocytes to locate within the T cell zone, although trafficking to the spleen was unaltered. Expression of CCL21 in lymphotoxin (LT)-α–deficient mice is dramatically reduced, however MCMV infection further reduced CCL21 levels, suggesting that viral modulation of CCL21 was independent of LTα signaling. Activation of LTβ-receptor signaling with an agonistic antibody partially restored CCL21 mRNA expression and redirected transferred T cells to the splenic T cell zone in MCMV-infected mice. These results indicate that virus-induced alterations in lymphoid tissues can occur through an LT-independent modulation of chemokine transcription, and targeting of the LT cytokine system can counteract lymphoid tissue remodeling by MCMV. |
| publisher |
Public Library of Science |
| publishDate |
2006 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1386719/ |
| _version_ |
1611380955191181312 |