scholarly journals Nitric oxide contributes to induction of innate immune responses to gram-negative bacteria in Drosophila

2003 ◽  
Vol 17 (1) ◽  
pp. 115-125 ◽  
Author(s):  
E. Foley
Blood ◽  
2020 ◽  
Author(s):  
Xinyu Yang ◽  
Xiaoye Cheng ◽  
Yiting Tang ◽  
Xianhui Qiu ◽  
Zhongtai Wang ◽  
...  

Bacterial infection not only stimulates innate immune responses but also activates the coagulation cascades. Over-activation of the coagulation system in bacterial sepsis leads to disseminated intravascular coagulation (DIC), a life-threatening condition. However, the mechanisms by which bacterial infection activates the coagulation cascade are not fully understood. Here we show that type 1 interferons (IFNs), widely expressed family of cytokines that orchestrate innate antiviral and antibacterial immunity, mediate bacterial infection-induced DIC through amplifying the release of high mobility box group box 1 (HMGB1) into the blood stream. Inhibition of the expression of type 1 IFNs, disruption of their receptor IFN-α/βR or downstream effector (e.g., HMGB1) uniformly decreased Gram-negative bacteria-induced DIC. Mechanistically, extracellular HMGB1 markedly increased the pro-coagulant activity of tissue factor (TF) by promoting the externalization of phosphatidylserine (PS) to the outer cell surface, where PS assembles a complex of cofactor-proteases of the coagulation cascades. These findings not only provide novel insights into the link between innate immune responses and coagulation, but also open a new avenue for developing novel therapeutic strategies to prevent DIC in sepsis.


2006 ◽  
Vol 41 (5) ◽  
pp. 447-454 ◽  
Author(s):  
Konrad Tietze ◽  
Alexander Dalpke ◽  
Sigfried Morath ◽  
Reinier Mutters ◽  
Klaus Heeg ◽  
...  

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Liuke Sun ◽  
Ruifang Shen ◽  
Sandeep K. Agnihotri ◽  
Yun Chen ◽  
Zhiwei Huang ◽  
...  

2018 ◽  
Vol 1 (6) ◽  
pp. e201800237 ◽  
Author(s):  
Connie Ross ◽  
Amy H Chan ◽  
Jessica Von Pein ◽  
Dave Boucher ◽  
Kate Schroder

Caspase-11 is a cytosolic sensor and protease that drives innate immune responses to the bacterial cell wall component, LPS. Caspase-11 provides defence against cytosolic Gram-negative bacteria; however, excessive caspase-11 responses contribute to murine endotoxic shock. Upon sensing LPS, caspase-11 assembles a higher order structure called the non-canonical inflammasome that enables the activation of caspase-11 protease function, leading to gasdermin D cleavage and cell death. The mechanism by which caspase-11 acquires protease function is, however, poorly defined. Here, we show that caspase-11 dimerization is necessary and sufficient for eliciting basal caspase-11 protease function, such as the ability to auto-cleave. We further show that during non-canonical inflammasome signalling, caspase-11 self-cleaves at site (D285) within the linker connecting the large and small enzymatic subunits. Self-cleavage at the D285 site is required to generate the fully active caspase-11 protease (proposed here to be p32/p10) that mediates gasdermin D cleavage, macrophage death, and NLRP3-dependent IL-1β production. This study provides a detailed molecular mechanism by which LPS induces caspase-11–driven inflammation and cell death to provide host defence against cytosolic bacterial infection.


2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.


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