An SopB-mediated immune escape mechanism of Salmonella enterica can be subverted to optimize the performance of live attenuated vaccine carrier strains.
Salmonellae have evolved several mechanisms to evade host clearance. Here, we describe the influence on bacterial immune escape of the effector protein SopB, which is translocated into the cytosol through a type III secretion system. Wild-type bacteria, as well as the sseC and aroA attenuated mutants exerted a stronger cytotoxic effect on dendritic cells (DC) than their SopB-deficient derivatives. Cells infected with the double sseC sopB, phoP sopB and aroA sopB mutants also exhibited higher expression of MHC, CD80, CD86 and CD54 molecules, and showed a stronger capacity to process and present an I-E(d)-restricted epitope from the influenza hemagglutinin (HA) to CD4+ cells from TCR-HA transgenic mice in vitro. The incorporation of an additional mutation into the sopB locus of the attenuated sseC, phoP and aroA mutants resulted in the stimulation of improved humoral and cellular immune responses following oral vaccination. The obtained results define a new potential immune escape strategy of this important pathogen, and also demonstrate that this mechanism can be subverted to optimize the immune responses elicited using Salmonella as a live vaccine carrier.
Link
Claudia
C
Department of Vaccinology, Division of Microbiology, GBF-German Research Centre for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany.
Ebensen
Thomas
T
Ständner
Lothar
L
Déjosez
Marion
M
Reinhard
Elena
E
Rharbaoui
Faiza
F
Guzmán
Carlos A
CA
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002470:Cell Survival; D003713:Dendritic Cells / Q000382:microbiology; D000939:Epitopes / Q000276:immunology; D005260:Female; D017353:Gene Deletion; D006389:Hemagglutinins, Viral / Q000276:immunology; D006649:Histocompatibility Antigens / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D022562:Salmonella Vaccines / Q000276:immunology*; D019779:Salmonella enterica / Q000276:immunology* / Q000472:pathogenicity; D014436:Typhoid-Paratyphoid Vaccines; D014614:Vaccines, Synthetic / Q000276:immunology
D015703:Antigens, CD; D001426:Bacterial Proteins; D000939:Epitopes; D006389:Hemagglutinins, Viral; D006649:Histocompatibility Antigens; D022562:Salmonella Vaccines; C502375:SseC protein, Salmonella typhimurium; D014436:Typhoid-Paratyphoid Vaccines; D014614:Vaccines, Synthetic; C087350:aroA Salmonella vaccine; C489224:SopB protein, Salmonella