The role of matricellular proteins in bacterial containment and in the induction of pathogen-specific adaptive immune responses is unknown. We studied the function of the matricellular protein secreted protein, acidic and rich in cysteine (SPARC/osteonectin) in the dissemination of locally injected Salmonella typhimurium and in the subsequent immune response. We show that SPARC was required for the development of organized acute inflammatory reactions with granuloma-like (GL) features and for the control of bacterial spreading to draining lymph nodes (DLNs). However, SPARC-related GL also inhibited dendritic cell (DC) migration to the DLNs and limited the development of adaptive immune response, thus conferring increased susceptibility to the pathogen. In SPARC-deficient mice, both DC migration and antigen-specific responses were restored against bacteria, leading to protective anti-S. typhimurium immunity. This highlights a new function of matricellular proteins in bacterial infection and suggests that initial containment of bacteria can have drawbacks.

Contrasting roles of SPARC-related granuloma in bacterial containment and in the induction of anti-Salmonella typhimurium immunity

M. Rescigno
2008-01-01

Abstract

The role of matricellular proteins in bacterial containment and in the induction of pathogen-specific adaptive immune responses is unknown. We studied the function of the matricellular protein secreted protein, acidic and rich in cysteine (SPARC/osteonectin) in the dissemination of locally injected Salmonella typhimurium and in the subsequent immune response. We show that SPARC was required for the development of organized acute inflammatory reactions with granuloma-like (GL) features and for the control of bacterial spreading to draining lymph nodes (DLNs). However, SPARC-related GL also inhibited dendritic cell (DC) migration to the DLNs and limited the development of adaptive immune response, thus conferring increased susceptibility to the pathogen. In SPARC-deficient mice, both DC migration and antigen-specific responses were restored against bacteria, leading to protective anti-S. typhimurium immunity. This highlights a new function of matricellular proteins in bacterial infection and suggests that initial containment of bacteria can have drawbacks.
2008
tumor-necrosis-factor; regulatory dendritic cells; mycobacterium-tuberculosis infection; extracellular-matrix; growth-factor; factor-alpha; endothelial-cells; tissue inhibitors; T-cells; in-vivo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11699/3811
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