B7-DC is a recently discovered member of the B7 family that binds to PD-1 and is selectively expressed by dendritic cells (DCs). It has been shown to either costimulate or inhibit T cell responses. To assess the role of B7-DC in DC–T cell interactions, DCs from B7-DC knockout (KO) mice were generated and compared with DCs from wild-type (WT) and B7–1/B7–2 double KO mice. B7–1/B7–2–deficient DCs, while strongly diminished in their ability to stimulate naive CD4+ T cells, nonetheless retain partial activity. DCs from B7-DC KO mice are diminished in their ability to activate CD4+ T cells, demonstrating that DC-expressed B7-DC serves a predominantly stimulatory rather than inhibitory function in the initiation of T cell responses. B7-DC costimulates expression of CD40L with faster kinetics than B7–1 and displays potent synergy with B7–1 and B7–2 for T cell proliferation and cytokine production, indicating that these B7 family members work in concert to stimulate T cells. Finally, costimulation with B7-DC alone or in conjunction with B7–1 is PD-1 independent, indicating that B7-DC costimulates T cells via a second receptor.
Aims
This study was performed to evaluate the efficacy of butanoic acid against bacterial pathogens including Acinetobacter baumannii and Staphylococcus pseudintermedius.
Methods and Results
Vegetative bacteria were exposed to butanoic acid in vitro and log reduction was quantified using viable count assays. The maximum (8 and 9) log inactivation was determined by qualitatively assaying for growth/no‐growth after a 48‐h incubation (37°C). Membrane integrity after exposure to butanoic acid was determined by propidium iodide staining, scanning electron microscopy, membrane depolarization and inductively coupled plasma analysis. Cytosolic pH was measured by 5‐(6‐)carboxyfluorescein succinimidyl ester.
Conclusions
Inhibitory concentrations of butanoic acid ranged between 11 and 21 mmol l−1 for Gram‐positive and Gram‐negative species tested. The maximum log reduction of A. baumannii was achieved with a 10‐s exposure of 0·50 mol l−1 of butanoic acid. Staphylococcus pseudintermedius required 0·40 mol l−1 of butanoic acid to achieve the same level of reduction in the same time period. Inactivation was associated with membrane permeability and acidification of the cytosol.
Significance and Impact of the Study
Antibiotic resistance among bacterial pathogens necessitates the utilization of novel therapeutics for disinfection and biological control. These results may facilitate the development of butanoic acid as an effective agent against a broad‐spectrum of antibiotic‐resistant bacterial pathogens.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.