Specific remodeling of splenic architecture by cytomegalovirus.

Abstract

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)-alpha-deficient mice is dramatically reduced, however MCMV infection further reduced CCL21 levels, suggesting that viral modulation of CCL21 was independent of LTalpha signaling. Activation of LTbeta-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.

• Authors: Chris A Benedict, Carl De Trez, Kirsten Schneider, Sukwon Ha, Ginelle Patterson, Carl F Ware
• Journal: PLoS pathogens (PLoS Pathog) Vol. 2 Issue 3 Pg. e16 (Mar 2006) ISSN: 1553-7374 [Electronic] United States
• PMID: 16518465 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Ccl21c protein, mouse
• Chemokine CCL21
• Chemokines, CC
• Ltbr protein, mouse
• Lymphotoxin beta Receptor
• Lymphotoxin-alpha
• RNA, Messenger
• Receptors, Tumor Necrosis Factor

Topics

• Animals
• Chemokine CCL21
• Chemokines, CC (antagonists & inhibitors, genetics)
• Cytomegalovirus (physiology)
• Cytomegalovirus Infections (metabolism, pathology, virology)
• Lymphotoxin beta Receptor
• Lymphotoxin-alpha (deficiency)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Molecular Sequence Data
• RNA, Messenger (metabolism)
• Receptors, Tumor Necrosis Factor (agonists, metabolism)
• Signal Transduction
• Spleen (metabolism, pathology, virology)
• T-Lymphocytes (pathology)