Gata6+ large peritoneal macrophages: an evolutionarily conserved sentinel and effector system for infection and injury

Salm, Lilian; Shim, Raymond; Noskovičová, Nina; Kubes, Paul

doi:10.1016/j.it.2022.12.002

Cited by 12 publications

(8 citation statements)

References 89 publications

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“…injection compared to sham controls after four (Figure 4H) and eight hours (Figure 4-figure supplement 1F) (Ghosn et al, 2010). Such LPM disappearance following abdominal E. coli infection is a result of free-floating clots composed of LPMs and neutrophils and important for effective pathogen clearance (Salm et al, 2023;Vega-Pérez et al, 2021;Zindel et al, 2021) but not dependent on ATP release according to our data. Interestingly, however, the number of small peritoneal macrophages (SPM) and CX3CR1 pos monocytes was significantly reduced, whereas neutrophils were significantly increased almost up to 8 hours (Figure 4I, Figure 4-figure supplement 1G) in bacterial ATP-depleted abdominal sepsis (PS+pAPY).…”

Section: Released Bacterial Atp Reduces Neutrophil Counts and Impairs...supporting

confidence: 66%

Released Bacterial ATP Shapes Local and Systemic Inflammation during Abdominal Sepsis

Spari,

Schmid,

Sánchez-Taltavull

et al. 2024

Preprint

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Sepsis causes millions of deaths per year worldwide and is a current global health priority declared by the WHO. Sepsis-related deaths are a result of dysregulated inflammatory immune responses indicating the need to develop strategies to target inflammation. An important mediator of inflammation is extracellular adenosine triphosphate (ATP) that is released by inflamed host cells and tissues, and also by bacteria in a strain-specific and growth-dependent manner. Here, we investigated the mechanisms by which bacteria release ATP. Using genetic mutant strains ofEscherichia coli(E. coli), we demonstrate that ATP release is dependent on ATP synthase within the inner bacterial membrane. In addition, impaired integrity of the outer bacterial membrane notably contributes to ATP release and is associated with bacterial death. In a mouse model of abdominal sepsis, local effects of bacterial ATP were analysed using a transformedE. colibearing an arabinose-inducible periplasmic apyrase hydrolyzing ATP to be released. Abrogating bacterial ATP release shows that bacterial ATP suppresses local immune responses, resulting in reduced neutrophil counts and impaired survival. In addition, bacterial ATP has systemic effects via its transport in outer membrane vesicles (OMV). ATP-loaded OMV are quickly distributed throughout the body and upregulated expression of genes activating degranulation in neutrophils, potentially contributing to the exacerbation of sepsis severity. This study reveals mechanisms of bacterial ATP release and its local and systemic roles in sepsis pathogenesis.

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Section: Released Bacterial Atp Reduces Neutrophil Counts and Impairs...supporting

confidence: 66%

Released Bacterial ATP Shapes Local and Systemic Inflammation during Abdominal Sepsis

Spari,

Schmid,

Sánchez-Taltavull

et al. 2024

Preprint

Self Cite

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“…Mature LPMs reside in the peritoneum with a less alternatively activated state, but once activated by signals derived from injury, they can be rapidly induced to express molecules associated with an alternative activated phenotype, which are thought to have tissue repair properties, showing decreased production of pro-inflammatory cytokines and increased production of immunosuppressive cytokines [ 9 , 35 ]. Our results suggested that Erastin-induced ferroptotic THP-1 cells enhanced LPM efferocytosis and promoted LPMs skewing themselves toward alternative or repair phenotype, since the level of pro-resolving factor-TGF-β1 was significantly upregulated, while the expressions of pro-inflammatory factors TNF-α, IL-1β, and IL-6 were significantly downregulated in LPMs cocultured with Erastin-treated THP-1 cells (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

MSCs promote the efferocytosis of large peritoneal macrophages to eliminate ferroptotic monocytes/macrophages in the injured endometria

Wang,

Li,

Yin

et al. 2024

Stem Cell Res Ther

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Background Endometria are one of the important components of the uterus, which is located in the peritoneal cavity. Endometrial injury usually leads to intrauterine adhesions (IUA), accompanied by inflammation and cell death. We previously reported that both the endometrial ferroptosis was increased and monocytes/macrophages were involved in endometrial injury of IUA. Large peritoneal macrophages (LPMs) are recently reported to migrate into the injured tissues and phagocytose dead cells to repair the tissues. We previously demonstrated that mesenchymal stromal cells (MSCs) had made excellent progress in the repair of endometrial injury. However, it is unclear whether MSCs regulate the LPM efferocytosis against ferroptotic monocytes/macrophages in the injured endometria. Methods Here, endometrial injury in IUA mouse model was conducted by uterine curettage and LPS injection surgery and the samples were collected at different times to detect the changes of LPMs and ferroptotic monocytes/macrophages. We conducted LPMs depletion assay in vivo and LPMs and Erastin-induced ferroptotic THP-1 cells coculture systems in vitro to detect the LPM efferocytosis against ferroptotic monocytes/macrophages. The IUA model was treated with MSCs, and their effects on LPMs and endometrial repair were analyzed. Flow cytometry, western blotting, quantitative real-time PCR, immunohistochemical analysis, ELISA, and RNA-sequencing were performed. Results We found that LPMs migrated to the injured uteri in response to the damage in early phase (3 h), and sustained to a later stage (7 days). Astonishingly, we found that ferroptotic monocytes/macrophages were significantly increased in the injured uteri since 12 h after injury. Moreover, LPMs cocultured with Erastin-induced ferroptotic THP-1 cells in vitro, efferocytosis of LPMs against ferroptotic monocytes/macrophages was emerged. The mRNA expression profiles revealed that LPM efferocytosis against ferroptotic monocytes/macrophages was an induction of glycolysis program and depended on the PPARγ-HK2 pathway. Importantly, we validated that MSCs promoted the efferocytic capability and migration of LPMs to the injured uteri via secreting stanniocalcin-1 (STC-1). Conclusion The data collectively demonstrated first the roles of LPMs via removal of ferroptotic monocytes/macrophages and provided a novel mechanism of MSCs in repairing the endometrial injury. Graphical Abstract

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“…Accumulating evidence highlighted that macrophage was involved in and initiated the inflammatory injury. 10,13 To uncover the underlying mechanism of SNS on ameliorating inflammatory injuries, we then wonder about the special immunocyte type that first infiltrated into the lungs and liver, which in turn can be targeted to SNS. To date, the effect of SNS on mediating immunocytes activities remains largely elusive.…”

Section: Discussionmentioning

confidence: 99%

“…Macrophages exhibit multiple and essential roles in inflammatory injury of the lungs, liver, and cardiovascular system and metabolic disease. 10,11 Macrophage-induced autoinflammation and injury mainly depended on regulating NLRP3-related inflammatory signalings. 12,13 Notch1-YAP loop positively contributes to macrophage M1-type polarization to exacerbate liver injury.…”

Section: Introductionmentioning

confidence: 99%

Sinensetin Attenuated Macrophagic NLRP3 Inflammasomes Formation via SIRT1-NRF2 Signaling

Lin,

Deng,

Gong

et al. 2023

ACS Omega

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Macrophage-mediated inflammation plays essential roles in multiple-organ injury. Sinensetin (SNS) at least exhibits anti-inflammation, antioxidant, and antitumor properties. However, the underlying mechanism of SNS-targeted macrophage-mediated inflammation remains elusive. In the present study, our results showed that SNS suppressed lipopolysaccharide (LPS)-induced inflammation to ameliorate lung and liver injuries. Mechanistically, SNS significantly inhibited M1-type macrophage polarization and its NLRP3 inflammasome formation to significantly decrease tumor necrosis factor α (TNFα) and IL-6 expression, while increasing IL-10 expression. Moreover, SNS interacted and activated SIRT1 to promote NRF2 and its target gene SOD2 transcription, which subsequently decreased LPS-induced inflammation. SIRT1 knockdown impaired the effects of SNS on the inhibition of macrophage polarization, NLRP3 inflammasome formation, and NRF2/SOD2 signaling. Taken together, our results showed that SNS is a potential and promising natural active ingredient to ameliorate inflammatory injury via activating SIRT1/NRF2/SOD2 signaling.

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Gata6+ large peritoneal macrophages: an evolutionarily conserved sentinel and effector system for infection and injury

Cited by 12 publications

References 89 publications

Released Bacterial ATP Shapes Local and Systemic Inflammation during Abdominal Sepsis

Released Bacterial ATP Shapes Local and Systemic Inflammation during Abdominal Sepsis

MSCs promote the efferocytosis of large peritoneal macrophages to eliminate ferroptotic monocytes/macrophages in the injured endometria

Sinensetin Attenuated Macrophagic NLRP3 Inflammasomes Formation via SIRT1-NRF2 Signaling

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