Biological Function Of Foamy Macrophages And Mechanism Of Inhibiting Wound Healing In Tuberculous Wound

Tuberculous wound is a kind of wound formed by Mycobacterium tuberculosis(MTB)invading local tissues of the body,resulting in necrosis of the invaded site or adjacent skin and subcutaneous soft tissue,and finally leading to skin ulceration.At present,there are still some problems to be solved in the diagnosis and treatment of tuberculous wounds,such as delayed healing and a high postoperative recurrence rate.The main cause of the above problems is the lack of understanding of its pathogenesis and the lag of research.Current research data show that monocyte-macrophages form foamy macrophages through various mechanisms,change the immune microenvironment of local tissues,and inhibit the normal functions of various cells.Therefore,we speculate that the formation of foamy macrophages is related to the difficulty of wound healing.Our previous observations found that a subtype of foamy macrophages that did not engulf MTB in the wound edge tissue of patients with recurrent tuberculous wounds,and its distribution characteristics and proportion might be closely related to wound healing.Foamy macrophages provide an "umbrella" for the survival of MTB.The study reported foamy macrophages that "infect" surrounding tissues form many new foamy macrophages by secreting mycolic acid,leading to the spread of the inflammatory response.It is well known that fibroblasts and vascular endothelial cells are key cells that affect the process of wound healing.In the wound microenvironment where fibroblasts,vascular endothelial cells,and foamy macrophages co-exist,will these three types of cells interact with each other,thereby affecting the healing process of tuberculous wounds?Whether the infection and spreading mechanism of foamy macrophages are related to the persistent and refractory wounds and easy relapse,what is the effect of the resulting foamy macrophages without MTB on the healing of tuberculous wounds,and whether the foamy macrophages without MTB have any effect on acute wounds negative effects of the healing process?In addition,could intervention in the related pathways that regulate foamy macrophages formation and reverse the process of refractory wound healing?None of the above issues has been reported in previous studies.Based on the previous research,this project intends to adopt the "effector cell-disease-wound microenvironment" thinking mode.From the clinicopathological characteristics,the interaction between foamy macrophages and fibroblasts/endothelial cells in vitro,the verification of animal wound models in vivo,and the validation of healing intervention experiments,these three aspects validate our hypothesis,thus systematically and comprehensively to reveal the mechanisms of refractory tuberculous wounds.