Mast cells aggravate sepsis by inhibiting peritoneal macrophage phagocytosis

Dahdah, Albert; Gautier, Grégory; Attout, Tarik; Fiore, Frédéric Di; Lebourdais, Emeline; Msallam, Rasha; Daëron, Marc; Monteiro, Renato C.; Benhamou, Marc; Charles, Nicolas; Davoust, Jean; Blank, Ulrich; Malissen, Bernard; Launay, Pierre

doi:10.1172/jci75212

Cited by 115 publications

(142 citation statements)

References 56 publications

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“…3B). As a control, DT injection alone in C57BL/6 wt mice did not alter renal architecture or cellularity of the normal tissue (data not shown), in agreement with previous data in other inflammatory models (23,31). It also did not affect kidney injury after acute IRI as judged by the equal increase in systemic creatinine levels 24 h post-IRI in PBS-or DT-treated C57BL/6 wt mice (Supplemental Fig.…”

Section: Aggravates Aki After Bilateral Irisupporting

confidence: 90%

“…Results show that 2 wk post-DT injection TdTomato + c-Kit 2 basophils had completely replenished and were found in equal numbers both in the bone marrow and in the blood in PBS-and DT-treated mice ( Fig. 2A), as reported before (23). In contrast, TdTomato + c-Kit + MCs were profoundly depleted both in the peritoneal cavity and in renal capsules at the time of surgery (Fig.…”

Section: Examination Of MC Depletion In Acute and Chronic Models Of Irisupporting

confidence: 78%

“…RMB mice (official name, B6;B6. Ms4a2 tm1Mal ) generation was described in Dahdah et al (23). The targeted allele of the Ms4a2 gene encoding the FcεRI b-chain in RMB mice included a cassette coding for the human DT receptor and the fluorescent protein TdTomato.…”

Section: Mouse Proceduresmentioning

confidence: 99%

“…Based on the above results showing rapid systemic and local (in renal capsules) activation of MCs after acute IRI, we sought to assess their overall role both in acute and chronic IRI using RMB mice, which allow DT-mediated ablation of MCs and basophils (23). Additionally, this mouse model allows distinguishing MCdriven activities during the early acute and late phases of the disease by choosing the appropriate timing of DT administration.…”

Section: Examination Of MC Depletion In Acute and Chronic Models Of Irimentioning

confidence: 99%

“…Recently, we have established a new model of MC deficiency, the red MC and basophil (RMB) mouse (23). This model, in addition to allowing visualization of fluorescent MCs in tissues, permits conditional ablation of MCs via diphtheria toxin (DT) injection.…”

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confidence: 99%

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Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia–Reperfusion Injury

Danelli

Madjène

Madera-Salcedo

et al. 2017

The Journal of Immunology

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Ischemia–reperfusion injury (IRI) is an important cause of acute kidney injury that can lead to end-stage renal failure. Although the ensuing inflammatory response can restore homeostasis, a consecutive maladaptive repair and persistent inflammation represent important risk factors for postischemic chronic kidney disease development. In this study, we investigated the role of mast cells in both the early and late phases of the inflammatory response in experimental models of acute and chronic renal IRI using our recently developed mouse model that allows conditional ablation of mast cells. Depletion of mast cells prior to IRI resulted in improved renal function due to diminished local inflammatory cytokine/chemokine levels and neutrophil recruitment to the kidneys after the acute injury phase (48 h post-IRI). Furthermore, although not completely protected, mast cell–depleted mice displayed less organ atrophy and fibrosis than did wild-type mice during the chronic phases (2 and 6 wk post-IRI) of disease development. Conversely, mast cell ablation after the acute phase of IRI had no impact on organ atrophy, tubular necrosis, or fibrosis. Thus, our results suggest a deleterious role of mast cells during the acute inflammatory phase of IRI promoting subsequent fibrosis development, but not during the chronic phase of the disease.

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Section: Aggravates Aki After Bilateral Irisupporting

confidence: 90%

Section: Examination Of MC Depletion In Acute and Chronic Models Of Irisupporting

confidence: 78%

Section: Mouse Proceduresmentioning

confidence: 99%

Section: Examination Of MC Depletion In Acute and Chronic Models Of Irimentioning

confidence: 99%

mentioning

confidence: 99%

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Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia–Reperfusion Injury

Danelli

Madjène

Madera-Salcedo

et al. 2017

The Journal of Immunology

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Near Infrared‐Triggered Nitric Oxide‐Release Nanovesicles with Mild‐Photothermal Antibacterial and Immunomodulation for Healing MRSA‐Infected Diabetic Wounds

Xu,

Zhang,

Zhang

et al. 2024

Adv Healthcare Materials

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Bacterial infection‐induced excessive inflammation is a major obstacle in diabetic wound healing. Nitric oxide (NO) exhibits significant antibacterial activity but is extremely deficient in diabetes. Hence, a near‐infrared (NIR)‐triggered NO release system is constructed through codelivery of polyarginine (PArg) and gold nanorods (Au) in an NIR‐activatable methylene blue (MB) polypeptide‐assembled nanovesicle (Au/PEL‐PBA‐MB/PArg). Upon NIR irradiation, the quenched MB in the nanovesicles is photoactivated to generate more reactive oxygen species (ROS) to oxidize PArg and release NO in an on‐demand controlled manner. With the specific bacterial capture of phenylboronic acid (PBA), NO elevated membrane permeability and boosted bacterial vulnerability in the photothermal therapy (PTT) of the Au nanorods, which is displayed by superior mild PTT antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA) at temperatures < 49.7 °C in vitro. Moreover, in vivo, the antibacterial nanovesicles greatly suppressed the burst of MRSA‐induced excessive inflammation, NO relayed immunomodulated macrophage polarization from M1 to M2, and the excessive inflammatory phase is successfully transferred to the repair phase. In cooperation with angiogenesis by NO, tissue regeneration is accelerated in MRSA‐infected diabetic wounds. Therefore, nanoplatform has considerable potential for accelerating the healing of infected diabetic wounds.

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Mouse Tissue‐Resident Peritoneal Macrophages in Homeostasis, Repair, Infection, and Tumor Metastasis

et al. 2023

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Large peritoneal macrophages (LPMs) are long-lived, tissue-resident macrophages, formed during embryonic life, developmentally and functionally confined to the peritoneal cavity. LPMs provide the first line of defense against life-threatening pathologies of the peritoneal cavity, such as abdominal sepsis, peritoneal metastatic tumor growth, or peritoneal injuries caused by trauma, or abdominal surgery. Apart from their primary phagocytic function, reminiscent of primitive defense mechanisms sustained by coelomocytes in the coelomic cavity of invertebrates, LPMs fulfill an essential homeostatic function by achieving an efficient clearance of apoptotic, that is crucial for the maintenance of self-tolerance. Research performed over the last few years, in mice, has unveiled the mechanisms by which LPMs fulfill a crucial role in repairing peritoneal injuries and controlling microbial and parasitic infections, reflecting that the GATA6-driven LPM transcriptional program can be modulated by extracellular signals associated with pathological conditions. In contrast, recent experimental evidence supports that peritoneal tumors can subvert LPM metabolism and function, leading to the acquisition of a tumor-promoting potential. The remarkable functional plasticity of LPMs can be nevertheless exploited to revert tumor-induced LPM protumor potential, providing the basis for the development of novel immunotherapeutic approaches against peritoneal tumor metastasis based on macrophage reprogramming.

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Mast cells aggravate sepsis by inhibiting peritoneal macrophage phagocytosis

Cited by 115 publications

References 56 publications

Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia–Reperfusion Injury

Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia–Reperfusion Injury

Near Infrared‐Triggered Nitric Oxide‐Release Nanovesicles with Mild‐Photothermal Antibacterial and Immunomodulation for Healing MRSA‐Infected Diabetic Wounds

Mouse Tissue‐Resident Peritoneal Macrophages in Homeostasis, Repair, Infection, and Tumor Metastasis

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