Publications by authors named "Denzel Middleton"
Rapamycin (rapa), an immunosuppressive medication, has demonstrated considerable effectiveness in reducing organ transplant rejection and treating select autoimmune diseases. However, the standard oral administration of rapa results in poor bioavailability, broad biodistribution, and harmful off-target effects, necessitating improved drug delivery formulations. Polymeric microparticles (MPs) are one such solution and have demonstrated promise in pre-clinical studies to improve the therapeutic efficacy of rapa.
View Article and Find Full Text PDFPathogen recognition is an essential component to achieve the desired outcome of host protection. Nod-like receptor pyrin containing domain 3 (NLRP3) is a cytoplasmic pattern recognition receptor (PRR) with a wide array of agonists, such as PAMPs, DAMPs, ATP, bacterial product and viral products. Stimulation of the NLRP3 inflammasome results in proteolytic activation of IL-1β and IL-18, cell pyroptosis and classically, the induction of proinflammatory responses.
View Article and Find Full Text PDFNew approaches to treat autoimmune diseases are needed, and we can be inspired by mechanisms in immune tolerance to guide the design of these approaches. Efferocytosis, the process of phagocyte-mediated apoptotic cell (AC) disposal, represents a potent tolerogenic mechanism that we could draw inspiration from to restore immune tolerance to specific autoantigens. ACs engage multiple avenues of the immune response to redirect aberrant immune responses.
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- Influenza virus outbreaks pose a significant global health challenge each year, with current vaccines often ineffective due to changes in the virus and low immune responses.
- COBRA hemagglutinin (HA) immunogens show promise in addressing viral mutations but require adjuvants to enhance their effectiveness, with STING agonists demonstrating potential in this role.
- This study explores a new vaccine platform using acetalated dextran microparticles with COBRA HA and a STING agonist in mouse models, revealing varying efficacy across different genetic backgrounds and health conditions, emphasizing the need for targeted adjuvant strategies.
Type 1 diabetes mellitus (T1D) is the leading metabolic disorder in children worldwide. Over time, incidence rates have continued to rise with 20 million individuals affected globally by the autoimmune disease. The current standard of care is costly and time-consuming requiring daily injections of exogenous insulin.
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- The study investigates immune activation in sheep's blood cells during Haemonchus contortus infection, focusing on two breeds with different resistance levels.
- Peripheral blood mononuclear cells (PBMC) from resistant St. Croix sheep showed a greater increase in immune-related gene expression (499 genes) compared to susceptible Suffolk sheep (130 genes), with 25 genes shared.
- St. Croix PBMC also displayed upregulation of pattern recognition receptors, suggesting enhanced immune recognition of the parasite, which may explain their ability to resist infection.
Host protective immunity to Haemonchus contortus (Hc) infection in parasite-resistant St. Croix (STC) sheep is initiated early and characterized by an influx of innate cells and robust interleukin-4 (IL-4) production, resulting in T-helper type 2 immune (Th2) responses. The purpose of these studies was to elucidate the source of early IL-4 production.
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