Sepsis Bacterial Publications (38473)
Sepsis Bacterial Publications
In this study, we show that NKG2D regulates B1a cell development and function. We find that mice deficient for NKG2D have a strong reduction of B1a cell numbers. As a result, NKG2D-deficient mice produce significantly less Ag-specific IgM Abs upon immunization with T cell-independent Ags, and they are more susceptible to Gram-negative sepsis. Klrk1(-/-) B1a cells are also functionally impaired and they fail to provide protection against Francisella novicida upon adoptive transfer. Using mixed bone marrow chimeric mice, we show that the impact of NKG2D deficiency on B1a cell development is cell intrinsic. No changes in homeostatic turnover and homing of B cells were detectable, limiting the effects of NKG2D to modulation of the hematopoietic development of B1a cells. Using conditional ablation, we demonstrate that the effect of NKG2D on B1a cell development occurs at a developmental stage that precedes the common lymphoid progenitor. Our findings reveal an unexpected new role for NKG2D in the regulation of B1a cell development. The protective effects of this activating receptor therefore reach beyond that of cytotoxic cells, stimulating the immune system to fight bacterial infections by promoting development of innate-like B cells.
During sepsis evolution it is supposed that microglial could exert both neurotoxic and repairing effects depending on the specific microglial phenotype assumed. In this context, here it was reviewed the role of microglial polarization during sepsis-associated brain dysfunction.
Cathelicidins are a class of antimicrobial peptide found in humans, mice, and rats, among others. Known as LL-37 in humans and cathelin-related antimicrobial peptide (CRAMP) in rodents, cathelicidins are produced by many different cells, including macrophages, neutrophils, and epithelial cells. The role of cathelicidins is somewhat confounding, as they exhibit both pro-and anti-inflammatory activity. A major obstacle in the study of cathelicidins is the inability of exogenous LL-37 or CRAMP to mimic the activity of their endogenous counterparts. Nevertheless, studies have shown that LL-37 is recognized by multiple receptors, and may stabilize or modulate Toll-like receptor signaling. In addition, cathelicidins play a role in apoptosis, inflammasome activation, and phagocytosis. However, many studies are revealing the dual effects of cathelicidins. For example, CRAMP appears to be protective in models of group A Streptococcus skin infection, pneumonia, and meningitis, but detrimental in cases of severe bacterial infection, such as septic shock. It is becoming increasingly clear that the activity of cathelicidins is modulated by complex interactions with the microenvironment, as well as the disease background. This article reviews what is currently known about the activity of cathelicidins in an attempt to understand their complex roles in systemic diseases.
Here we report that BLP-tolerised macrophages exhibited accelerated phagosome maturation and enhanced bactericidal activity upon bacterial infection, with upregulated expression of membrane-trafficking regulators and lysosomal enzymes. Notably, bacterial challenge resulted in a strong activation of NF-κB pathway in BLP-tolerised macrophages. Importantly, activation of NF-κB pathway is critical for BLP tolerance-enhanced antimicrobial activity, as deactivation of NF-κB in BLP-tolerised macrophages impaired phagosome maturation and intracellular killing of the ingested bacteria. Finally, activation of NF-κB pathway in BLP-tolerised macrophages was dependent on NOD1 and NOD2 signalling, as knocking-down NOD1 and NOD2 substantially inhibited bacteria-induced activation of NF-κB and overexpression of Rab10 and Acp5, two membrane-trafficking regulators and lysosomal enzymes contributed to BLP tolerance-enhanced bactericidal activity. These results indicate that activation of NF-κB pathway is essential for BLP tolerance-augmented antimicrobial activity in innate phagocytes and depends primarily on both NOD1 and NOD2.
Picroside II treatment enhanced bacterial clearance in septic mice. Further, picroside II treatment alleviated the inflammatory response in sepsis and enhanced immune function by inhibiting the activation of NLRP3 inflammasome and NF-κB pathways. Picroside II may represent an anti-inflammatory drug candidate, providing novel insight into the treatment of sepsis.
Microbiology and clinical data were collected for SJS/TEN patients admitted to our Burn Centre from January 2010 through January 2016.
A total of 24 patients were admitted over the study period. There were 303 bacterial cultures taken whereof 113 (37.3%) were positive (median of 4.4 per patient). Twenty-two (91.7%) patients had at least one positive sample recorded. Fifteen (62.5%) patients had a confirmed episode of sepsis with skin being the most common source of colonization (77.8%). Eleven (45.8%) patients received empiric antibiotic therapy at referral facility/prior to admission to our Centre. Patients who grew a higher number of different species were significantly less likely to have received early empiric antimicrobial therapy (P < .001).
Secondary bacterial infection and sepsis were a highly common finding in our patient population. Despite the risk of resistance and further immunological provocation, empirical antibiotic treatment might have a place in clinical management.
NETs were critical for the development of sepsis-induced intravascular coagulation regardless of the inciting bacterial stimulus (Gram-negative, Gram-positive, or bacterial products). Removal of NETs via DNase infusion, or in peptidylarginine deiminase-4 (PAD4)-deficient mice (which have impaired NETs production), resulted in significantly lower quantities of intravascular thrombin activity, reduced platelet aggregation, and improved microvascular perfusion. NETs-induced intravascular coagulation was dependent on a collaborative interaction between histone H4 in NETs, platelets, and the release of inorganic polyphosphate. Real-time perfusion imaging revealed markedly improved microvascular perfusion in response to blockade of NETs-induced coagulation, which correlated with reduced markers of systemic intravascular coagulation and end-organ damage in septic mice. Together, these data demonstrate for the first time in an in vivo model of infection, a dynamic NETs-platelets-thrombin axis that promotes intravascular coagulation and microvascular dysfunction in sepsis.
Gardnerella vaginalis and Staphylococcus saprophyticus dominated the abscesses. Phylogenomic analyses of ancient, historical, and contemporary data showed that G. vaginalis Troy fell within contemporary genetic diversity, whereas S. saprophyticus Troy belongs to a lineage that does not appear to be commonly associated with human disease today. We speculate that the ecology of S. saprophyticus infection may have differed in the ancient world as a result of close contacts between humans and domesticated animals. These results highlight the complex and dynamic interactions with our microbial milieu that underlie severe maternal infections.
This study was established to determine whether burn injury has long-term clinical impacts on patients' immune responses.
Using a population-based retrospective longitudinal study and linked hospital morbidity and death data from Western Australia, comparative rates of hospitalisation for respiratory infections in burn patients and a non-injured comparator cohort were assessed. In addition, a mouse model of non-severe burn injury was also used in which viral respiratory infection was induced at 4 weeks post-injury using a mouse modified version of the Influenza A virus (H3NN; A/mem/71-a).
The burn injured cohort contained 14893 adult patients from 1980-2012 after removal of those patients with evidence of smoke inhalation or injury to the respiratory tract. During the study follow-up study a total of 2,884 and 2,625 respiratory infection hospital admissions for the burn and uninjured cohorts, respectively, were identified. After adjusting for covariates, the burn cohort experienced significantly elevated admission rates for influenza and viral pneumonia (IRR, 95%CI: 1.73, 1.27-2.36), bacterial pneumonia (IRR, 95%CI: 2.05, 1.85-2.27) and for other types of upper and lower respiratory infections (IRR, 95% CI: 2.38, 2.09-2.71). In the mouse study an increased viral titre was observed after burn injury, accompanied by a reduced CD8 response and increased NK and NKT cells in the draining lymph nodes. This data suggests burn patients are at long-term increased risk of infection due to sustained modulation of the immune response.
Severe sepsis was induced in male ICR mice (n = 7) via the CLP procedure. The effects of chrysin and kaempferol combination treatment on septic mice were investigated using a 7-day survival study. The levels of key proinflammatory mediators and markers-such as aspartate aminotransferase (AST), TNF-α, and NO-in the sera samples of the septic mice were determined via ELISA and fluorescence determination at different time point intervals post-CLP challenge. Liver tissue samples from septic mice were harvested to measure myeloperoxidase (MPO) levels using a spectrophotometer. Moreover, intraperitoneal fluid (IPF) bacterial clearance and total leukocyte count were also assessed to detect any antibacterial effects exerted by chrysin and kaempferol, individually and in combination. Kaempferol treatment improved the survival rate of CLP-challenged mice by up to 16%. During this treatment, kaempferol expressed antibacterial, antiapoptotic and antioxidant activities through the attenuation of bacterial forming units, AST and NO levels, and increased polymorphonuclear leukocyte (PMN) count in the IPF. On the other hand, the chrysin treatment significantly reduced serum TNF-α levels. However, it failed to significantly improve the survival rate of the CLP-challenged mice. Subsequently, the kaempferol/chrysin combination treatment significantly improved the overall 7-day survival rate by 2-fold-up to 29%. Kaempferol and chrysin revealed some synergistic effects by acting individually upon multiple pathophysiological factors involved during sepsis. Although the kaempferol/chrysin combination did not exhibit significant antibacterial effects, it did exhibit anti-inflammatory and antioxidant activities, which translate to significant improvement in the survival rate of septic animals. These findings suggest the potential application of this combination treatment as a beneficial adjuvant supplement strategy in sepsis control.