Immune Intervention in Sepsis

Chen, Jian; Wei, Haiming

doi:10.3389/fphar.2021.718089

Cited by 39 publications

(34 citation statements)

References 200 publications

(218 reference statements)

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“…Due to the concomitant paralyzed immune system, the host’s ability to eradicate the invading microbes is severely compromised, which opens the way for late infections to develop and leads to unresolved organ failure. Hence, a prolonged and disorganized host hypoinflammatory response/immune paralysis is also detrimental and contributes to the increased risk of death in sepsis [ 34 , 35 ]. On top of the extensive involvement of an overactive host defense response, the importance of microcirculation dysfunction, coagulation impairment, mitochondrial damage, endoplasmic reticulum stress, cellular alterations and organ–organ crosstalk is also becoming increasingly evident and recognized [ 24 , 25 ] ( Figure 1 ).…”

Section: Pathophysiology Of Sepsismentioning

confidence: 99%

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Zhu

Chambers

Zeng

et al. 2022

IJMS

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Sepsis, a potentially lethal condition resulting from failure to control the initial infection, is associated with a dysregulated host defense response to pathogens and their toxins. Sepsis remains a leading cause of morbidity, mortality and disability worldwide. The pathophysiology of sepsis is very complicated and is not yet fully understood. Worse still, the development of effective therapeutic agents is still an unmet need and a great challenge. Gases, including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), are small-molecule biological mediators that are endogenously produced, mainly by enzyme-catalyzed reactions. Accumulating evidence suggests that these gaseous mediators are widely involved in the pathophysiology of sepsis. Many sepsis-associated alterations, such as the elimination of invasive pathogens, the resolution of disorganized inflammation and the preservation of the function of multiple organs and systems, are shaped by them. Increasing attention has been paid to developing therapeutic approaches targeting these molecules for sepsis/septic shock, taking advantage of the multiple actions played by NO, CO and H2S. Several preliminary studies have identified promising therapeutic strategies for gaseous-mediator-based treatments for sepsis. In this review article, we summarize the state-of-the-art knowledge on the pathophysiology of sepsis; the metabolism and physiological function of NO, CO and H2S; the crosstalk among these gaseous mediators; and their crucial effects on the development and progression of sepsis. In addition, we also briefly discuss the prospect of developing therapeutic interventions targeting these gaseous mediators for sepsis.

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Section: Pathophysiology Of Sepsismentioning

confidence: 99%

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Zhu

Chambers

Zeng

et al. 2022

IJMS

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“…After infection, and in the early sepsis stage, macrophages are activated through TLR [ 13 ] and differentiate into M1 by activating NF-κB, which drives the release of large amounts of pro-inflammatory cytokines, such as TNF-α, IL-1, IL-6, and IL-8 [ 12 ]. In this stage, host defense is promoted to eliminate invading pathogen or damaged tissues [ 14 ]. Then, in the late phase, macrophages polarize to the M2 phenotype by repressing NF-κB activation via the p50 NF-κB subunit to dampen the pro-inflammatory response [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Macrophage Polarization and Reprogramming in Acute Inflammation: A Redox Perspective

2022

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Macrophage polarization refers to the process by which macrophages can produce two distinct functional phenotypes: M1 or M2. The balance between both strongly affects the progression of inflammatory disorders. Here, we review how redox signals regulate macrophage polarization and reprogramming during acute inflammation. In M1, macrophages augment NADPH oxidase isoform 2 (NOX2), inducible nitric oxide synthase (iNOS), synaptotagmin-binding cytoplasmic RNA interacting protein (SYNCRIP), and tumor necrosis factor receptor-associated factor 6 increase oxygen and nitrogen reactive species, which triggers inflammatory response, phagocytosis, and cytotoxicity. In M2, macrophages down-regulate NOX2, iNOS, SYNCRIP, and/or up-regulate arginase and superoxide dismutase type 1, counteract oxidative and nitrosative stress, and favor anti-inflammatory and tissue repair responses. M1 and M2 macrophages exhibit different metabolic profiles, which are tightly regulated by redox mechanisms. Oxidative and nitrosative stress sustain the M1 phenotype by activating glycolysis and lipid biosynthesis, but by inhibiting tricarboxylic acid cycle and oxidative phosphorylation. This metabolic profile is reversed in M2 macrophages because of changes in the redox state. Therefore, new therapies based on redox mechanisms have emerged to treat acute inflammation with positive results, which highlights the relevance of redox signaling as a master regulator of macrophage reprogramming.

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“…Sepsis is a life-threatening organ dysfunction mainly caused by an abnormal infection-induced immune response. [1][2][3][4] In the excessive inflammatory response stage of sepsis, the immune response to sepsis may further cause cell and tissue injury or multiple organ dysfunction syndrome (MODS) with high morbidity and mortality. [5][6][7] In recent years, the incidence rate of sepsis has increased worldwide.…”

Section: Introductionmentioning

confidence: 99%

Neutrophils inhibit CD8⁺T cells immune response by arginase-1 signaling in patients with sepsis

Dai¹,

Ding²,

Tan³

et al. 2022

World Journal of Emergency Medicine

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BACKGROUND: Patients with sepsis often exhibit an acute inflammatory response, followed by an immunosuppressive phase with a poor immune response. However, the underlying mechanisms have not been fully elucidated. METHODS:We sought to comprehensively characterize the transcriptional changes in neutrophils of patients with sepsis by transcriptome sequencing. Additionally, we conducted a series of experiments, including real-time quantitative polymerase chain reaction (RT-qPCR) and flow cytometry to investigate the role of arginase-1 signaling in sepsis. RESULTS:Through the analysis of gene expression profiles, we identified that the negative regulation of T cell activation signaling was enriched, and the expression of arginase-1 was high in neutrophils from patients with sepsis. Furthermore, we conducted flow cytometry and found that the function of CD8 + T cells in septic patients was impaired. Moreover, neutrophils from septic patients inhibited the percentage of polyfunctional effector CD8 + T cells through arginase-1. Additionally, the proportions of granzyme B + IFNγ + CD8 + T and TNFα + IFNγ + CD8 + T cells increased after inhibition of arginase-1 signaling. CONCLUSION:The impaired effector function of CD8 + T cells could be restored by blocking arginase-1 signaling in patients with sepsis.

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Immune Intervention in Sepsis

Cited by 39 publications

References 200 publications

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Macrophage Polarization and Reprogramming in Acute Inflammation: A Redox Perspective

Neutrophils inhibit CD8⁺T cells immune response by arginase-1 signaling in patients with sepsis

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Immune Intervention in Sepsis

Cited by 39 publications

References 200 publications

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Macrophage Polarization and Reprogramming in Acute Inflammation: A Redox Perspective

Neutrophils inhibit CD8+T cells immune response by arginase-1 signaling in patients with sepsis

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Product

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Neutrophils inhibit CD8⁺T cells immune response by arginase-1 signaling in patients with sepsis