Survival of Salmonella enterica serovar Typhimurium within late endosomal-lysosomal compartments of B lymphocytes is associated with the inability to use the vacuolar alternative major histocompatibility complex class I antigen-processing pathway.
Gamma interferon (IFN-gamma)-activated macrophages use an alternative processing mechanism to present Salmonella antigens to CD8(+) T lymphocytes. This pathway involves processing of antigen in a vacuolar compartment followed by secretion and loading of antigenic peptides to major histocompatibility complex class I (MHC-I) molecules on macrophage cell surface and bystander cells. In this study, we have shown that B lymphocytes are not able to process Salmonella antigens using this alternative pathway. This is due to differences in Salmonella enterica serovar Typhimurium-containing vacuoles (SCV) when comparing late endosomal-lysosomal processing compartments in B lymphocytes to those in macrophages. The IFN-gamma-activated IC21 macrophage cell line and A-20 B-cell line were infected with live or dead Salmonella enterica serovar Typhimurium. The SCV in B cells were in a late endosomal-lysosomal compartment, whereas SCV in macrophages were remodeled to a non-characteristic late endosomal-lysosomal compartment over time. Despite the difference in SCV within macrophages and B lymphocytes, S. enterica serovar Typhimurium survives more efficiently within the IFN-gamma-activated B cells than in activated macrophage cell lines. Similar results were found during in vivo acute infection. We determined that a lack of remodeling of late endosomal-lysosomal compartments by live Salmonella infection in B lymphocytes is associated with the inability to use the alternative MHC-I antigen-processing pathway, providing a survival advantage to the bacterium. Our data also suggest that the B lymphocyte late endosome-lysosome environment allows the expression of Salmonella virulence mechanisms favoring B lymphocytes in addition to macrophages and dendritic cells as a reservoir during in vivo infection.
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados (CINVESTAV), Av. IPN No. 2508, Colonia San Pedro Zacatenco, Delegación Gustavo A. Madero, México, DF CP 07360, Mexico.
Roberto
R
Rosales-Reyes
Celia
C
Alpuche-Aranda
María de la Luz
Mde L
Ramírez-Aguilar
Angel Denisse
AD
Castro-Eguiluz
Vianney
V
Ortiz-Navarrete
D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000382:microbiology* / Q000648:ultrastructure; D002460:Cell Line; D011992:Endosomes / Q000382:microbiology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology; D008247:Lysosomes / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012486:Salmonella typhimurium / Q000254:growth & development*; D014617:Vacuoles / Q000276:immunology / Q000382:microbiology*
D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma