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

Gianluca Rotta, Gianluca Matteoli, Elisa Mazzini, Paolo Nuciforo, Mario P. Colombo, Maria Rescigno

Research output: Contribution to journalArticle

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. JEM

Original languageEnglish
Pages (from-to)657-667
Number of pages11
JournalJournal of Experimental Medicine
Volume205
Issue number3
DOIs
Publication statusPublished - Mar 17 2008

ASJC Scopus subject areas

  • Immunology

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