| RRC ID |
83719
|
| Author |
Zechini L, Todd H, Sanchez T, Tudor DR, Campbell JS, Antonian E, Jenkins SJ, Lucas CD, Davidson AJ, van den Elsen J, Schumacher LJ, Scopelliti A, Wood W.
|
| Title |
Drosophila complement-like Mcr acts as a wound-induced inflammatory chemoattractant.
|
| Journal |
Curr Biol
|
| Abstract |
Sterile tissue injury is accompanied by an acute inflammatory response whereby innate immune cells rapidly migrate to the site of injury guided by pro-inflammatory chemotactic damage signals released at the wound. Understanding this immune response is key to improving human health, and recent advances in imaging technology have allowed researchers using different model organisms to observe this inflammatory response in vivo. Over recent decades, offering a unique combination of live time-lapse microscopy and genetics, the fruit fly Drosophila has emerged as a powerful model system to study inflammatory cell migration within a living animal.1,2,3,4 However, we still know relatively little regarding the identity of the earliest signals that drive this immune cell recruitment and the mechanisms by which they act within the complex, in vivo setting of a multicellular organism. Here, we couple the powerful genetics and live imaging of Drosophila with mathematical modeling to identify the fly complement ortholog-macroglobulin complement-related (Mcr)-as an early, wound-induced chemotactic signal responsible for the inflammatory recruitment of immune cells to injury sites in vivo. We show that epithelial-specific knockdown of Mcr suppresses the recruitment of macrophages to wounds and combine predictive mathematical modeling with in vivo genetics to understand macrophage migration dynamics following manipulation of this chemoattractant. We propose a model whereby Mcr operates alongside hydrogen peroxide to ensure a rapid and efficient immune response to damage, uncovering a novel function for this protein that parallels the chemotactic role of the complement component C5a in mammals.
|
| Volume |
35(7)
|
| Pages |
1656-1664.e4
|
| Published |
2025-4-7
|
| DOI |
10.1016/j.cub.2025.02.036
|
| PII |
S0960-9822(25)00200-3
|
| PMID |
40107264
|
| MeSH |
Animals
Chemotactic Factors* / metabolism
Chemotaxis*
Complement System Proteins* / genetics
Complement System Proteins* / metabolism
Drosophila Proteins* / genetics
Drosophila Proteins* / metabolism
Drosophila melanogaster* / genetics
Drosophila melanogaster* / immunology
Drosophila melanogaster* / physiology
Inflammation
Macrophages / immunology
Wound Healing*
|
| IF |
9.601
|
| Resource |
| Drosophila |
DGRC#109007 |
