CCR2-dependent CX3CR1+ colonic macrophages promote Enterococcus faecalis dissemination

Enterococci are Gram-positive commensal bacteria found in the gastrointestinal tract of most mammals. Although enterococci are typically non-pathogenic, they are intrinsically resistant to cephalosporin antibiotics, and treatment with cephalosporins can lead to opportunistic infections in humans and mice (1, 2). Currently, enterococci are the third leading cause of infectious endocarditis, with Enterococcus faecalis contributing to >90% of reported enterococcus-related cases (3, 4). Furthermore, the rising prevalence of vancomycin-resistant enterococci, predominantly Enterococcus faecium, has made enterococci a leading cause of hospital-acquired infections in the United States (5). Nevertheless, most individuals colonized with enterococci, including E. faecalis or E. faecium, do not succumb to infections (6, 7). This highlights the generally commensal nature of enterococci but suggests a gap in our understanding of the preconditions for opportunistic infections by these pathobionts. To date, the mechanisms by which commensal enterococci subvert host immunity to become pathogenic remain poorly understood.