Salmonella Typhimurium increases functional PD-L1 synergistically with IFNγ in intestinal epithelial cells viaSalmonellaPathogenicity Island-2.

5 years ago

Salmonella Typhimurium increases functional PD-L1 synergistically with IFNγ in intestinal epithelial cells viaSalmonellaPathogenicity Island-2.

C Altier, J M Sahler, C R Eade, J C March

Non-typhoidal serovars ofSalmonella entericaare pathogenic bacteria that are common causes of food poisoning. WhereasSalmonellamechanisms of host cell invasion, inflammation, and pathogenesis are mostly well-established, a new possible mechanism of immune evasion is being uncovered. PD-L1 is an immunosuppressive membrane protein that binds to activated T cells via their PD-1 receptor and thereby halts their activation. PD-L1 expression plays an essential role in immunological tolerance of self, but is also exploited for immune evasion by pathogen-infected cells and cancer cells. Here, we show for the first time thatSalmonellainfection of intestinal epithelial cells causes induction of PD-L1. The increased expression of PD-L1 throughSalmonellainfection was seen in both human and rat intestinal epithelial cell lines. We determined that cellular invasion by the bacteria is necessary for PD-L1 induction, potentially indicating thatSalmonellaare delivering mediators from inside the host cell that trigger the increased PD-L1 expression. Using knockout mutants, we determined that this effect largely originates from theSalmonellaPathogenicity Island-2. We also show for the first time in any cell type, thatSalmonellacombined with IFNγ causes a synergistic induction of PD-L1. Finally, we show thatSalmonellaplus IFNγ induction of PD-L1 decreased cytokine production of activated T cells. UnderstandingSalmonellaimmune evasion strategies could generate new therapeutic targets and help to manipulate PD-L1 expression in other diseases.

Publisher URL: http://doi.org/10.1128/IAI.00674-17

DOI: 10.1128/IAI.00674-17