Abstract
Recruitment of bone marrow derived monocytes via bloodstream and their subsequent conversion to CX3CR1+ macrophages in response to intestinal injury is dependent on CCR2, Nr4a1, and the microbiome. This process is critical for proper tissue repair; however, GATA6+ peritoneal cavity macrophages might represent an alternative, more readily available source of mature and functional myeloid cells at the damaged intestinal locations. Here we show, using spinning-disk confocal microscopy, that large F4/80hiGATA6+ peritoneal cavity macrophages promptly accumulate at damaged intestinal sites upon intestinal thermal injury and upon dextran sodium sulfate induced colitis in mice via a direct route from the peritoneal cavity. In contrast to bloodstream derived monocytes/macrophages, cavity macrophages do not depend on CCR2, Nr4a1 or the microbiome for recruitment, but rather on the ATP-release and exposed hyaluronan at the site of injury. They participate in the removal of necrotic cells, revascularization and collagen deposition and thus resolution of tissue damage. In summary, peritoneal cavity macrophages represent a rapid alternative route of intestinal tissue repair to traditional monocyte-derived macrophages.
Highlights
Recruitment of bone marrow derived monocytes via bloodstream and their subsequent conversion to CX3CR1+ macrophages in response to intestinal injury is dependent on CCR2, Nr4a1, and the microbiome
We examined the recruitment of monocytes and macrophages in response to sterile thermal injury of the intestine using Cx3cr1GFP/+Ccr2RFP/+ mice
Tissue-resident CX3CR1+ macrophages do not move during intestinal injury and depend on classical CCR2+ monocytes to be recruited and to convert to CX3CR1+ monocytes/macrophages
Summary
Recruitment of bone marrow derived monocytes via bloodstream and their subsequent conversion to CX3CR1+ macrophages in response to intestinal injury is dependent on CCR2, Nr4a1, and the microbiome. This process is critical for proper tissue repair; GATA6+ peritoneal cavity macrophages might represent an alternative, more readily available source of mature and functional myeloid cells at the damaged intestinal locations. In contrast to bloodstream derived monocytes/macrophages, cavity macrophages do not depend on CCR2, Nr4a1 or the microbiome for recruitment, but rather on the ATP-release and exposed hyaluronan at the site of injury They participate in the removal of necrotic cells, revascularization and collagen deposition and resolution of tissue damage. The mammalian intestinal tract is populated with over 100 trillion microbes, the majority of which reside in the colon[13,14] so they could be a potent recruitment cue for peritoneal macrophages
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
