Staphylococcal phosphatidylglycerol antigens activate human T cells via CD1a.
Nature immunology
Expressed on epidermal Langerhans cells, CD1a presents a range of self-lipid antigens found within the skin; however, the extent to which CD1a presents microbial ligands from bacteria colonizing the skin is unclear. Here we identified CD1a-dependent T cell responses to phosphatidylglycerol (PG), a ubiquitous bacterial membrane phospholipid, as well as to lysylPG, a modified PG, present in several Gram-positive bacteria and highly abundant in Staphylococcus aureus. The crystal structure of the CD1a-PG complex showed that the acyl chains were buried within the A'- and F'-pockets of CD1a, while the phosphoglycerol headgroup remained solvent exposed in the F'-portal and was available for T cell receptor contact. Using lysylPG and PG-loaded CD1a tetramers, we identified T cells in peripheral blood and in skin that respond to these lipids in a dose-dependent manner. TetramerCD4 T cell lines secreted type 2 helper T cell cytokines in response to phosphatidylglycerols as well as to co-cultures of CD1a dendritic cells and Staphylococcus bacteria. The expansion in patients with atopic dermatitis of CD4 CD1a-(lysyl)PG tetramer T cells suggests a response to lipids made by bacteria associated with atopic dermatitis and provides a link supporting involvement of PG-based lipid-activated T cells in atopic dermatitis pathogenesis.
10.1038/s41590-022-01375-z
Emerging role of the host microbiome in neuropsychiatric disorders: overview and future directions.
Molecular psychiatry
The human body harbors a diverse ecosystem of microorganisms, including bacteria, viruses, and fungi, collectively known as the microbiota. Current research is increasingly focusing on the potential association between the microbiota and various neuropsychiatric disorders. The microbiota resides in various parts of the body, such as the oral cavity, nasal passages, lungs, gut, skin, bladder, and vagina. The gut microbiota in the gastrointestinal tract has received particular attention due to its high abundance and its potential role in psychiatric and neurodegenerative disorders. However, the microbiota presents in other body tissues, though less abundant, also plays crucial role in immune system and human homeostasis, thus influencing the development and progression of neuropsychiatric disorders. For example, oral microbiota imbalance and associated periodontitis might increase the risk for neuropsychiatric disorders. Additionally, studies using the postmortem brain samples have detected the widespread presence of oral bacteria in the brains of patients with Alzheimer's disease. This article provides an overview of the emerging role of the host microbiota in neuropsychiatric disorders and discusses future directions, such as underlying biological mechanisms, reliable biomarkers associated with the host microbiota, and microbiota-targeted interventions, for research in this field.
10.1038/s41380-023-02287-6
Sodium in the microenvironment regulates immune responses and tissue homeostasis.
Müller Dominik N,Wilck Nicola,Haase Stefanie,Kleinewietfeld Markus,Linker Ralf A
Nature reviews. Immunology
During tissue inflammation, immune cells infiltrate the interstitial space of target organs, where they sense and adapt to local environmental stimuli. Such stimuli include not only pathogens but also local factors such as the levels of oxygenation, nutrients and electrolytes. An important electrolyte in this regard is sodium (Na). Recent in vivo findings have shown a role of Na storage in the skin for electrolyte homeostasis. Thereby, Na intake may influence the activation status of the immune system through direct effects on T helper cell subsets and innate immune cells in tissues such as the skin and other target organs. Furthermore, high Na intake has been shown to alter the composition of the intestinal microbiota, with indirect effects on immune cells. The results suggest regulatory roles for Na in cardiovascular disease, inflammation, infection and autoimmunity.
10.1038/s41577-018-0113-4