CCR2-dependent CX3CR1+ colonic macrophages promote Enterococcus faecalis dissemination

Infect Immun. 2024 May 7;92(5):e0000624. doi: 10.1128/iai.00006-24. Epub 2024 Apr 17.

Abstract

Enterococci are common commensal bacteria that colonize the gastrointestinal tracts of most mammals, including humans. Importantly, these bacteria are one of the leading causes of nosocomial infections. This study examined the role of colonic macrophages in facilitating Enterococcus faecalis infections in mice. We determined that depletion of colonic phagocytes resulted in the reduction of E. faecalis dissemination to the gut-draining mesenteric lymph nodes. Furthermore, we established that trafficking of monocyte-derived CX3CR1-expressing macrophages contributed to E. faecalis dissemination in a manner that was not reliant on CCR7, the conventional receptor involved in lymphatic migration. Finally, we showed that E. faecalis mutants with impaired intracellular survival exhibited reduced dissemination, suggesting that E. faecalis can exploit host immune cell migration to disseminate systemically and cause disease. Our findings indicate that modulation of macrophage trafficking in the context of antibiotic therapy could serve as a novel approach for preventing or treating opportunistic infections by disseminating enteric pathobionts like E. faecalis.

Keywords: CCR2; CX3CR1; Enterococcus faecalis; colon; commensal; dissemination; gut-associated lymphoid tissue; macrophages; migration; pathobiont.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CX3C Chemokine Receptor 1* / genetics
  • CX3C Chemokine Receptor 1* / metabolism
  • Colon* / immunology
  • Colon* / microbiology
  • Enterococcus faecalis*
  • Gram-Positive Bacterial Infections / immunology
  • Gram-Positive Bacterial Infections / microbiology
  • Lymph Nodes / immunology
  • Lymph Nodes / microbiology
  • Macrophages* / immunology
  • Macrophages* / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Receptors, CCR2* / genetics
  • Receptors, CCR2* / metabolism
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / metabolism
  • Receptors, Chemokine* / genetics
  • Receptors, Chemokine* / metabolism

Substances

  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse
  • Receptors, CCR2
  • Receptors, Chemokine
  • Ccr2 protein, mouse
  • Receptors, CCR7