Contrasting roles of SPARC-related granuloma in bacterial containment and in the induction of anti-Salmonella typhimurium immunity.
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.
Rotta
Gianluca
G
Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy.
Matteoli
Gianluca
G
Mazzini
Elisa
E
Nuciforo
Paolo
P
Colombo
Mario P
MP
Rescigno
Maria
M
D000818:Animals; D001428:Bacterial Vaccines / Q000494:pharmacology; D002465:Cell Movement; D024141:Collagen Type IV / Q000378:metabolism; D015169:Colony Count, Microbial; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology / Q000502:physiology; D006099:Granuloma / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015676:Osteonectin / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology
D001428:Bacterial Vaccines; D024141:Collagen Type IV; D015676:Osteonectin