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 / G. Rotta, G. Matteoli, E. Mazzini, P. Nuciforo, M.P. Colombo, M. Rescigno. - In: JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 0022-1007. - 205:3(2008), pp. 657-667.
|Titolo:||Contrasting roles of SPARC-related granuloma in bacterial containment and in the induction of anti-Salmonella typhimurium immunity|
RESCIGNO, MARIA (Corresponding)
|Parole Chiave:||tumor-necrosis-factor; regulatory dendritic cells; mycobacterium-tuberculosis infection; extracellular-matrix; growth-factor; factor-alpha; endothelial-cells; tissue inhibitors; T-cells; in-vivo|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||2008|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1084/jem.20071734|
|Appare nelle tipologie:||01 - Articolo su periodico|