sepsis
Bacterial InfectionsEctopic Expression of Human Thymosin β4 Confers Resistance to Legionella pneumophila during Pulmonary and Systemic Infection in MiceThymosin beta-4 (Tβ4) is an actin-sequestering peptide that plays important roles in regeneration and remodeling of injured tissues. However, its function in a naturally occurring pathogenic bacterial infection model has remained elusive.
Host Response and InflammationRegulation of the Nfkbiz Gene and Its Protein Product IkBζ in Animal Models of Sepsis and Endotoxic ShockSepsis is a life-threatening condition that arises from a poorly regulated inflammatory response to pathogenic organisms. Current treatments are limited to antibiotics, fluid resuscitation, and other supportive therapies.
Bacterial InfectionsTargeting Neuropilin-1 Suppresses the Stability of CD4+ CD25+ Regulatory T Cells via the NF-κB Signaling Pathway in SepsisNeuropilin-1 (Nrp-1) contributes to maintaining the stability of CD4+ CD25+ regulatory T cells (Tregs). We investigated the impact of Nrp-1 on the stability of CD4+ CD25+ Tregs, and the underlying signaling pathways, in a model of sepsis. Splenic CD4+ CD25+ Tregs were either treated with anti-Nrp-1, transfected to silence Nrp-1 and...
Molecular PathogenesisAntibody Binding and Complement-Mediated Killing of Invasive Haemophilus influenzae Isolates from Spain, Portugal, and the NetherlandsHaemophilus influenzae is a Gram-negative bacterium that can be classified into typeable (types a through f) and nontypeable (NTHi) groups. This opportunistic pathogen asymptomatically colonizes the mucosal epithelium of the upper respiratory tract, from where it spreads to other neighboring regions, potentially leading to disease. Infection with NTHi can cause otitis...
Minireview | SpotlightCan the Cecal Ligation and Puncture Model Be Repurposed To Better Inform Therapy in Human Sepsis?A recent report by the National Institutes of Health on sepsis research has implied there is a trend to move away from mouse models of sepsis. The most commonly used animal model to study the pathogenesis of human sepsis is cecal ligation and puncture (CLP) in mice. The model has been the mainstay of sepsis research for decades and continues to be considered the gold standard to inform novel pathways of sepsis physiology and its...
MinireviewRole of β2 Integrins in Neutrophils and SepsisSepsis remains medically challenging, with high morbidity and mortality. A novel intervention is urgently needed in the absence of specific, targeted therapy. Neutrophils act as double-edged swords in sepsis; they can help to eradicate microbes, but they also contribute to tissue injury. β2 integrins are critical adhesion molecules that regulate a number of neutrophil functions. β2 integrins consist of four members, namely, αLβ2, αMβ2,...
Host Response and InflammationInflammatory Monocytes and Neutrophils Regulate Streptococcus suis-Induced Systemic Inflammation and Disease but Are Not Critical for the Development of Central Nervous System Disease in a Mouse Model of InfectionStreptococcus suis is an important porcine bacterial pathogen and zoonotic agent responsible for sudden death, septic shock, and meningitis. These pathologies are a consequence of elevated bacterial replication leading to exacerbated and uncontrolled inflammation, a hallmark of the S. suis systemic...
Host Response and InflammationElevated Levels of Interleukin-27 in Early Life Compromise Protective Immunity in a Mouse Model of Gram-Negative Neonatal SepsisNeonates are at increased risk for bacterial sepsis. We established that the immune-suppressive cytokine interleukin-27 (IL-27) is elevated in neonatal mice. Similarly, human cord blood-derived macrophages express IL-27 genes and secrete more cytokine than macrophages from adults. In the present work, we hypothesized that increased levels of IL-27 predispose neonatal mice to more severe infection during Gram-negative sepsis. Serum IL-27...
Host Response and InflammationInterleukin 17 Receptor E (IL-17RE) and IL-17C Mediate the Recruitment of Neutrophils during Acute Streptococcus pneumoniae PneumoniaNeutrophils contribute to lung injury in acute pneumococcal pneumonia. The interleukin 17 receptor E (IL-17RE) is the functional receptor for the epithelial-derived cytokine IL-17C, which is known to mediate innate immune functions. The aim of this study was to investigate the contribution of IL-17RE/IL-17C to pulmonary inflammation in a mouse model of acute Streptococcus...
Host Response and InflammationNF-κB RelA Is Required for Hepatoprotection during Pneumonia and SepsisPneumonia and sepsis are distinct but integrally linked public health concerns. The hepatic acute-phase response (APR), which is largely dependent on transcription factors NF-κB RelA and STAT3, is a hallmark of these pathologies and other injurious conditions. Inactivation of the APR can promote liver injury, a frequently observed organ dysfunction during sepsis. However, whether or how the acute-phase changes promote liver tissue...