Publications by authors named "Darren Higgins"

Article Synopsis
  • Innate immune pattern recognition receptors, like Toll-like receptors (TLRs), play a crucial role in the immune response to infections and influence our understanding of health and disease.
  • Researchers engineered macrophages to study the myddosome, a critical component of TLR signaling, revealing its dynamic nature and the formation of barrel-like structures that help recruit essential proteins.
  • The findings suggest that myddosomes are vital for TLR signaling and that some pathogens, like Listeria monocytogenes, can evade this immune response during their spread between cells.
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Aben, HGJ, Hills, SP, Higgins, D, Cooke, CB, Davis, D, Jones, B, and Russell, M. The efficacy of a multimodal recovery strategy implemented after a high-intensity rugby league training session. J Strength Cond Res 37(8): 1634-1642, 2023-The efficacy of a multimodal recovery strategy implemented within 4 hours of rugby league (RL) training was investigated using repeated-measures, randomized, crossover methods in 10 professional academy RL players (age: 17 ± 1 years).

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The type I interferon (IFN) signaling pathway has important functions in resistance to viral infection, with the downstream induction of interferon stimulated genes (ISG) protecting the host from virus entry, replication and spread. Listeria monocytogenes (Lm), a facultative intracellular foodborne pathogen, can exploit the type I IFN response as part of their pathogenic strategy, but the molecular mechanisms involved remain unclear. Here we show that type I IFN suppresses the antibacterial activity of phagocytes to promote systemic Lm infection.

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Sticholysins (Sts) I and II (StI and StII) are pore-forming proteins (PFPs), purified from the Caribbean Sea anemone Stichodactyla helianthus. StII encapsulated into liposomes induces a robust antigen-specific cytotoxic CD8 T lymphocytes (CTL) response and in its free form the maturation of bone marrow-derived dendritic cells (BM-DCs). It is probable that the latter is partially supporting in part the immunomodulatory effect on the CTL response induced by StII-containing liposomes.

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The NOX2 NADPH oxidase (NOX2) produces reactive oxygen species to kill phagosome-confined bacteria. However, we previously showed that is able to avoid the NOX2 activity in phagosomes and escape to the cytosol. Thus, despite the established role of NOX2 limiting infection in mice, the underlying mechanisms of this antibacterial activity remain unclear.

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In professional academy rugby league (RL) players, this two-part study examined; A) the within- and between-day reliability of isometric mid-thigh pulls (IMTP), countermovement jumps (CMJ), and a wellness questionnaire ( = 11), and B) profiled the responses with acceptable reliability (no between-trial differences and between-day coefficient of variation (CV) ≤10% and intraclass correlation coefficient (ICC) ≥0.8) for 120 h (baseline: -3, +24, +48, +72, +96, +120 h) following RL match-play ( = 10). In part A, force at 200, and 250 ms, and peak force (PF) demonstrated acceptable within- (CV%: 3.

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Listeria monocytogenes is an intracellular pathogen responsible for listeriosis, a foodborne disease that can lead to life-threatening meningitis. The 2011 L. monocytogenes cantaloupe outbreak was among the deadliest foodborne outbreaks in the United States.

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Plasma membrane integrity is essential for the viability of eukaryotic cells. In response to bacterial pore-forming toxins, disrupted regions of the membrane are rapidly repaired. However, the pathways that mediate plasma membrane repair are unclear.

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Cross-presentation is an important mechanism for the differentiation of effector cytotoxic T lymphocytes (CTL) from naïve CD8 T-cells, a key response for the clearance of intracellular pathogens and tumors. The liposomal co-encapsulation of the pore-forming protein sticholysin II (StII) with ovalbumin (OVA) (Lp/OVA/StII) induces a powerful OVA-specific CTL activation and an anti-tumor response . However, the pathway through which the StII contained in this preparation is able to induce antigen cross-presentation and the type of professional antigen presenting cells (APCs) involved have not been elucidated.

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is a facultative intracellular bacterial pathogen that is frequently associated with food-borne infection. Of particular concern is the ability of to breach the blood-brain barrier, leading to life-threatening meningitis and encephalitis. The mechanisms used by bacterial pathogens to infect the brain are not fully understood.

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is a Gram-positive intracellular pathogen that causes a severe invasive disease. Upon infecting a host cell, upregulates the transcription of numerous factors necessary for productive infection. VirR is the response regulator component of a two-component regulatory system in In this report, we have identified the putative ABC transporter encoded by genes as necessary for VirR function.

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is a common food-borne pathogen that can disseminate from the intestine and infect multiple organs. Here, we used sequence tag-based analysis of microbial populations (STAMP) to investigate population dynamics during infection. We created a genetically barcoded library of murinized and then used deep sequencing to track the pathogen's dissemination routes and quantify its founding population () sizes in different organs.

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Article Synopsis
  • Vaccine strategies are facing challenges in enhancing CD8 T cell responses due to the need for antigens to bypass cellular membranes for better presentation in antigen-presenting cells (APCs).
  • A new approach using sticholysin II (StII), a pore-forming protein from a Caribbean sea anemone, shows promise; it was encapsulated with ovalbumin (OVA) in liposomes to improve CTL activation and memory response in mice.
  • The study found that mice treated with the OVA-StII liposomes had stronger anti-tumor effects and CTL responses, indicating that StII may also help mature dendritic cells and function as an effective adjuvant in vaccine development.
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Type I interferons (IFNs) play a critical role in antiviral immune responses, but can be deleterious to the host during some bacterial infections. Listeria monocytogenes (Lm) induces a type I IFN response by activating cytosolic antiviral surveillance pathways. This is beneficial to the bacteria as mice lacking the type I IFN receptor (IFNAR1 ) are resistant to systemic infection by Lm.

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Chlamydia trachomatis is the causative agent of the most frequently reported bacterial sexually transmitted infection, the total burden of which is underestimated due to the asymptomatic nature of the infection. Untreated C. trachomatis infections can cause significant morbidities, including pelvic inflammatory disease and tubal factor infertility (TFI).

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Listeria monocytogenes is an intracellular bacterial pathogen that can replicate in the cytosol of host cells. These bacteria undergo actin-based motility in the cytosol via expression of ActA, which recruits host actin-regulatory proteins to the bacterial surface. L.

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Listeria monocytogenes is a Gram-positive, food-borne pathogen of humans and animals. L. monocytogenes is considered to be a potential public health risk by the U.

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The Gram-positive bacterium Listeria monocytogenes is a facultative intracellular pathogen whose virulence depends on its ability to spread from cell to cell within an infected host. Although the actin-related protein 2/3 (Arp2/3) complex is necessary and sufficient for Listeria actin tail assembly, previous studies suggest that other actin polymerization factors, such as formins, may participate in protrusion formation. Here, we show that Arp2/3 localized to only a minor portion of the protrusion.

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Efferocytosis, the process by which dying or dead cells are removed by phagocytosis, has an important role in development, tissue homeostasis and innate immunity. Efferocytosis is mediated, in part, by receptors that bind to exofacial phosphatidylserine (PS) on cells or cellular debris after loss of plasma membrane asymmetry. Here we show that a bacterial pathogen, Listeria monocytogenes, can exploit efferocytosis to promote cell-to-cell spread during infection.

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Vaccines are the most cost-effective means of preventing infectious diseases and have the potential to be used in a therapeutic capacity for the treatment of numerous chronic diseases and cancer. The majority of available vaccines function by eliciting antibodies that can neutralize toxins or opsonize the pathogen leading to elimination by professional phagocytes. However, there are many infectious and non-infectious diseases for which there are no available vaccines or the current antibody-mediated vaccines offer insufficient protection.

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Listeria monocytogenes is a Gram-positive, facultative intracellular pathogen capable of causing severe invasive disease with high mortality rates in humans. While previous studies have largely elucidated the bacterial and host cell mechanisms necessary for invasion, vacuolar escape, and subsequent cell-to-cell spread, the L. monocytogenes factors required for rapid replication within the restrictive environment of the host cell cytosol are poorly understood.

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Listeria monocytogenes is a bacterial pathogen that can escape the phagosome and replicate in the cytosol of host cells during infection. We previously observed that a population (up to 35%) of L. monocytogenes strain 10403S colocalize with the macroautophagy marker LC3 at 1 h postinfection.

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Carcinoembryonic antigen cell adhesion molecule like I (CEACAM1) is expressed on activated T cells and signals through either a long (L) cytoplasmic tail containing immune receptor tyrosine based inhibitory motifs, which provide inhibitory function, or a short (S) cytoplasmic tail with an unknown role. Previous studies on peripheral T cells show that CEACAM1-L isoforms predominate with little to no detectable CEACAM1-S isoforms in mouse and human. We show here that this was not the case in tissue resident T cells of intestines and gut associated lymphoid tissues, which demonstrated predominant expression of CEACAM1-S isoforms relative to CEACAM1-L isoforms in human and mouse.

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A comprehensive proteomic screening technology was previously used to characterize T cell responses to Chlamydia trachomatis infection. In this study, we demonstrated that T cells specific for protein antigens identified through this comprehensive technology home to the site of infection after mucosal challenge with C. trachomatis.

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Macrophages are immune cells that participate in the host defense against bacterial pathogens. These cells mediate bacterial clearance by internalizing bacteria into a phagosome, which ultimately fuses with lysosomes to kill bacteria. One bacterial strategy to evade killing in the phagosome is to escape from this compartment prior to lysosomal fusion.

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