Macrophage metabolism: a wound‐healing perspective

Caputa, George; Flachsmann, Lea J.; Cameron, Alanna M.

doi:10.1111/imcb.12237

Cited by 31 publications

(31 citation statements)

References 78 publications

(218 reference statements)

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“…At present, interactions between metabolism and the immune system (immunometabolism) are receiving increasing attention in research on human diseases (Boura‐Halfon et al., 2019; Caputa et al., 2019; Wang, Luan, et al., 2019).…”

Section: Discussionmentioning

confidence: 99%

Climate change facilitates a parasite’s host exploitation via temperature‐mediated immunometabolic processes

Scharsack

Wieczorek

Schmidt‐Drewello

et al. 2020

Global Change Biology

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Global climate change can influence organismic interactions like those between hosts and parasites. Rising temperatures may exacerbate the exploitation of hosts by parasites, especially in ectothermic systems. The metabolic activity of ectotherms is strongly linked to temperature and generally increases when temperatures rise. We hypothesized that temperature change in combination with parasite infection interferes with the host's immunometabolism. We used a parasite, the avian cestode Schistocephalus solidus, which taps most of its resources from the metabolism of an ectothermic intermediate host, the three-spined stickleback. We experimentally exposed sticklebacks to this parasite, and studied liver transcriptomes 50 days after infection at 13°C and 24°C, to assess their immunometabolic responses. Furthermore, we monitored fitness parameters of the parasite and examined immunity and body condition of the sticklebacks at 13°C, 18°C and 24°C after 36, 50 and 64 days of infection. At low temperatures (13°C), S. solidus growth was constrained, presumably also by the more active stickleback's immune system, thus delaying its infectivity for the final host to 64 days. Warmer temperature (18°C and 24°C) enhanced S. solidus growth, and it became infective to the final host already after 36 days. Overall, S. solidus produced many more viable offspring after development at elevated temperatures. In contrast, stickleback hosts had lower body conditions, and their immune system was less active at warm temperature. The stickleback's liver transcriptome revealed that mainly metabolic processes were differentially regulated between temperatures, whereas immune genes were not strongly affected. Temperature effects on gene expression were strongly enhanced in infected sticklebacks, and even in exposed-but-not-infected hosts. These data suggest that the parasite exposure in concert with rising temperature, as to be expected with global climate change, shifted the host's immunometabolism, thus providing nutrients for the enormous growth of the parasite and, at the same time suppressing immune defence.

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Section: Discussionmentioning

confidence: 99%

Climate change facilitates a parasite’s host exploitation via temperature‐mediated immunometabolic processes

Scharsack

Wieczorek

Schmidt‐Drewello

et al. 2020

Global Change Biology

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“…Macrophages are considered as the primary effector cells in regulating wound healing, unregulated macrophage activation represent a source of excessive in ammation, leading to aberrant wound healing (23)(24)(25). MDSCs have the potential to differentiate to macrophages in chronic in ammation (26).…”

Section: Ink128 Inhibits High Glucose-induced Differentiation Of Mdscmentioning

confidence: 99%

mTOR Inhibitor INK128 Promotes Wound Healing by Regulating MDSCs

Liu

et al. 2020

Preprint

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Background: Skin wounds in diabetic patients are hardly to recover. Accumulating evidence has shown that mammalian target of rapamycin (mTOR) pathway and myeloid-derived suppressor cells (MDSCs) are involved in inflammatory-related response. INK128 is a novel mTOR kinase inhibitor in clinical development. However, the exact roles of MDSCs and INK128 in healing wound of diabetic patients are unclear. Methods: Mice models of normal, diabetic, and diabetic+INK128 were constructed. Bone marrow (BM)-derived macrophages and RAW264.7 cell line co-cultured with MDSCs, which were induced at different conditions. Flow cytometry, western blot, quantitative real-time PCR, and immunohistochemical analysis were performed. Results: Diabetic mice (DM) had a slower recovery rate, thinner epidermal and dermal, and less blood vessels than those of normal mice. MDSCs were abnormally accumulated in DM and mTOR was activated in MDSCs of DM and the cells treat with high glucose. Moreover, mTOR signaling inhibitor INK128 could promote wound healing through reducing the MDSCs. MDSCs function was disordered in DM and high glucose environments, while INK128 could help retrieve their function. Furthermore, high glucose and other factors in DM could promote M-MDSCs differentiation to M1 pro-inflammatory macrophage cells, thus inhibiting wound healing. The differentiation, which was dependent on mTOR signaling, could be reversed by INK128. Conclusion: INK128 is potential to be developed as a clinical strategy to promote wound healing of diabetic patients.

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“…Macrophages are considered as the primary effector cells in regulating wound healing, unregulated macrophage activation represent a source of excessive in ammation, leading to aberrant wound healing [8,35,36]. MDSCs have the potential to differentiate to macrophages in chronic in ammation [37].…”

Section: Ink128 Inhibits High Glucose-induced Differentiation Of Mdscmentioning

confidence: 99%

mTOR inhibitor INK128 promotes diabetic wound healing by regulating MDSCs

Li¹,

Xu²,

Liu³

et al. 2020

Preprint

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Background: Skin wounds in diabetic patients are hardly to recover. Accumulating evidence has shown that mammalian target of rapamycin (mTOR) pathway and myeloid-derived suppressor cells (MDSCs) are involved in inflammation-related response. INK128 is a novel mTOR kinase inhibitor in clinical development. However, the exact roles of MDSCs and INK128 in healing wound of diabetic patients are unclear.Methods: Mice models of normal, diabetic, and diabetic+INK128 were constructed. Bone marrow (BM)-derived macrophages and RAW264.7 cell line co-cultured with MDSCs, which were induced at different conditions. Flow cytometry, western blot, quantitative real-time PCR, and immunohistochemical analysis were performed.Results: Diabetic mice (DM) had a slower recovery rate, thinner epidermal and dermal, and less blood vessels than those of normal mice. MDSCs were abnormally accumulated in DM and mTOR was activated in MDSCs from DM or treated with high glucose. Moreover, mTOR signaling inhibitor INK128 could promoted wound healing through reducing the MDSCs. MDSCs function was disordered in DM and high glucose environments, while INK128 could help retrieve their function. Furthermore, high glucose and other factors in DM could promote M-MDSCs differentiation to M1 pro-inflammatory macrophage cells, thus inhibiting wound healing. The differentiation, which was dependent on mTOR signaling, could be reversed by INK128.Conclusion: INK128 is potential to be developed as a clinical strategy to promote wound healing of diabetic patients.

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Macrophage metabolism: a wound‐healing perspective

Cited by 31 publications

References 78 publications

Climate change facilitates a parasite’s host exploitation via temperature‐mediated immunometabolic processes

Climate change facilitates a parasite’s host exploitation via temperature‐mediated immunometabolic processes

mTOR Inhibitor INK128 Promotes Wound Healing by Regulating MDSCs

mTOR inhibitor INK128 promotes diabetic wound healing by regulating MDSCs

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