Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210, USA.
Published: July 2012
AI Article Synopsis
Article Abstract
Inflammasomes are multiprotein complexes that include members of the NLR (nucleotide-binding domain leucine-rich repeat containing) family and caspase-1. Once bacterial molecules are sensed within the macrophage, the inflammasome is assembled, mediating the activation of caspase-1. Caspase-11 mediates caspase-1 activation in response to lipopolysaccharide and bacterial toxins, and yet its role during bacterial infection is unknown. Here, we demonstrated that caspase-11 was dispensable for caspase-1 activation in response to Legionella, Salmonella, Francisella, and Listeria. We also determined that active mouse caspase-11 was required for restriction of L. pneumophila infection. Similarly, human caspase-4 and caspase-5, homologs of mouse caspase-11, cooperated to restrict L. pneumophila infection in human macrophages. Caspase-11 promoted the fusion of the L. pneumophila vacuole with lysosomes by modulating actin polymerization through cofilin. However, caspase-11 was dispensable for the fusion of lysosomes with phagosomes containing nonpathogenic bacteria, uncovering a fundamental difference in the trafficking of phagosomes according to their cargo.
African American (AA) women are disproportionally affected by obesity and hyperlipidemia, particularly in the setting of adverse social determinants of health (aSDoH) contributing to health disparities. Obesity, hyperlipidemia, and aSDoH appear to impair Natural Killer cells (NKs). As potential common underlying mechanisms are largely unknown, we sought to investigate common signaling pathways involved in NK dysfunction related to obesity and hyperlipidemia in AA women from under-resourced neighborhoods.
The recent surge in emerging viral infections warrants the design of broad-spectrum antivirals. We aim to develop a lead molecule that targets a common biochemical feature of many enveloped viruses, membrane fusion. To achieve the broad-spectrum ability, instead of targeting the fusion machinery, we plan to modulate the physicochemical properties of the host and viral membranes to block fusion.
The mechanistic target of rapamycin complex 1 (mTORC1) functions as a master regulator of cell growth and proliferation. We previously demonstrated that intracellular calcium ion (Ca) concentration modulates the mTORC1 pathway via binding of the Ca sensor protein calmodulin (CaM) to tuberous sclerosis complex 2 (TSC2), a critical negative regulator of mTORC1. However, the precise molecular mechanism by which Ca/CaM modulates mTORC1 activity remains unclear.
Macroautophagy, a universal cellular process, sends cellular material to lysosomes for breakdown and is often activated by stressors like hypoxia or drug exposure. It is vital for protein balance, neurotransmitter release, synaptic function, and neuron survival. The role of macroautophagy in substance use disorders is dual.
is the etiologic agent of trichomoniasis, one of the most common non-viral sexually transmitted infections globally. Our previous work reported the role of phosphatidylinositol 4,5-bisphosphates (PIP) signaling in the actin-dependent pathogenicity of . This study further demonstrated that iron transiently regulated phosphatidylinositol-4-phosphate 5-kinase (PI4P5K) proteostasis and its complex formation with an active ADP ribosylation factor Arf220, facilitating co-trafficking to the plasma membrane, crucial for PIP production.
