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The discovery of mammalian TLRs (Toll-like receptors), first identified in 1997 based on their homology with Drosophila Toll, greatly altered our understanding of how the innate immune system recognizes and responds to diverse microbial pathogens. TLRs are evolutionarily conserved type I transmembrane proteins expressed in both immune and non-immune cells,(More)
During the past 10 years, much attention has been focused towards elucidating the impact of Toll-like receptors (TLRs) in central nervous system (CNS) innate immunity. TLR signaling triggers the transcriptional activation of pro-interleukin-1β (pro-IL-1β) and pro-IL-18 that are processed into their active forms by the inflammasome. Recent studies have(More)
Biofilms are complex communities of bacteria encased in a matrix composed primarily of polysaccharides, extracellular DNA, and protein. Staphylococcus aureus can form biofilm infections, which are often debilitating due to their chronicity and recalcitrance to antibiotic therapy. Currently, the immune mechanisms elicited during biofilm growth and their(More)
Biofilms are adherent communities of bacteria contained within a complex matrix. Although host immune responses to planktonic staphylococcal species have been relatively well-characterized, less is known regarding immunity to staphylococcal biofilms and how they modulate anti-bacterial effector mechanisms when organized in this protective milieu.(More)
The potent phagocytic and microbicidal activities of neutrophils and macrophages are among the first lines of defense against bacterial infections. Yet Staphylococcus aureus is often resistant to innate immune defense mechanisms, especially when organized as a biofilm. To investigate how S. aureus biofilms respond to macrophages and neutrophils, gene(More)
Biofilm infections often lead to significant morbidity due to their chronicity and recalcitrance to antibiotics. We have demonstrated that methicillin-resistant Staphylococcus aureus (MRSA) biofilms can evade macrophage (MΦ) antibacterial effector mechanisms by skewing MΦs toward an alternatively activated M2 phenotype. To overcome this immune evasion, we(More)
Bacterial biofilms represent a significant therapeutic challenge based on their ability to evade host immune and antibiotic-mediated clearance. Recent studies have implicated IL-1β in biofilm containment, whereas Toll-like receptors (TLRs) had no effect. This is intriguing, since both the IL-1 receptor (IL-1R) and most TLRs impinge on MyD88-dependent(More)
Lung cancer, the leading cause of cancer-related deaths worldwide, is a heterogeneous disease comprising multiple histologic subtypes that harbor disparate mutational profiles. Immune-based therapies have shown initial promise in the treatment of lung cancer patients but are limited by low overall response rates. We sought to determine whether the host(More)
Biofilms are adherent communities of bacteria contained within a complex matrix. Staphylococcal species are frequent etiological agents of device-associated biofilm infections in humans that are highly recalcitrant to antimicrobial therapy and alter host immune responses to facilitate bacterial persistence. Here we describe a mouse model of(More)
Natural antimicrobial peptides (AMPs) are promising candidates for developing a generation of new antimicrobials to meet the challenge of antibiotic-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). To facilitate the search for new candidates, we have utilised the Antimicrobial Peptide Database (APD), which contains natural(More)