Survival ofSalmonella entericaSerovar 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

Abstract

Gamma interferon (IFN-␥)-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-␥-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 noncharacteristic 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-␥-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.

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

“…BALB/c mice were intraperitoneally infected with fifty bacteria, either Salmonella WT-GFP or Salmonella Δ sopB- GFP, as established in our previous work [42,43]. Eighteen hours post-infection, we evaluated Akt activation and YAP phosphorylation in splenic B cells using flow cytometry.…”

Salmonella Downregulates Nod-like Receptor Family CARD Domain Containing Protein 4 Expression To Promote Its Survival in B Cells by Preventing Inflammasome Activation and Cell Death

“…Hence, the downregulation of NLRC4 in B cells may also have an impact on Salmonella replication and phagosomal maturation. Indeed, we have observed that Salmonella resides in a lysosomal compartment, and large numbers of bacteria are recovered from this compartment (8).…”

“…In fact, Salmonella survives more efficiently within B cells than in macrophages, and it can be recovered from splenic B cells, bone marrow B cell precursors, and plasma cells after a single-dose inoculation (8). However, the mechanisms used by Salmonella to survive within B cells are not established.…”

“…Furthermore, it has been demonstrated that B cells are required for priming the CD4 + and CD8 + T cell responses during infection (3). However, B cells have additional roles during Salmonella infection, and there is evidence that Salmonella infects B cells in vivo and in vitro (3)(4)(5)(6)(7)(8)(9). Within B cells, Salmonella resides in a late endosomal compartment that is distinct from the Salmonella-containing vacuoles observed in macrophages (8).…”

“…However, B cells have additional roles during Salmonella infection, and there is evidence that Salmonella infects B cells in vivo and in vitro (3)(4)(5)(6)(7)(8)(9). Within B cells, Salmonella resides in a late endosomal compartment that is distinct from the Salmonella-containing vacuoles observed in macrophages (8). In addition, the bacteria infect B cell precursors in the bone marrow, and these cells may serve as reservoirs of Salmonella infection (10).…”