Staphyloccocus aureusbiofilm, in the absence of planktonic bacteria, produces factors that activate counterbalancing inflammatory and immune-suppressive genes in human monocytes

Abstract

AbstractStaphyloccocus aureus(S. aureus) is a major bacterial pathogen in orthopedic periprosthetic joint infection (PJI).S. aureusforms biofilms that promote persistent infection by shielding bacteria from immune cells and inducing an antibiotic-resistant metabolic state. We developed an in vitro system to studyS. aureusbiofilm interactions with primary human monocytes in the absence of planktonic bacteria. In line with previous in vivo data,S. aureusbiofilm induced expression of inflammatory genes such asTNFandIL1B, and their anti-inflammatory counter-regulator IL-10.S. aureusbiofilm also activated expression of PD-1 ligands that suppress T cell function, and of IL-1RA that suppresses differentiation of protective Th17 cells. Gene induction did not require monocyte:biofilm contact and was mediated by a soluble factor(s) produced by biofilm-encased bacteria that was heat resistant and > 3 kD in size. Activation of suppressive genes by biofilm was sensitive to suppression by Jak inhibition. These results support an evolving paradigm that biofilm plays an active role in modulating immune responses, and suggest this occurs via production of a soluble vita-PAMP. Induction of T cell suppressive genes byS. aureusbiofilm provides insights into mechanisms that suppress T cell immunity in PJI, and suggest that anti-PD-1 therapy that is modeled on immune checkpoint blockade for tumors may be beneficial in PJI.