Biology subjects

Lichtenberger, S.

Publications and source records attributed to Lichtenberger, S..

3 recordsLinked to original sources

bioRxiv2026

Natural Killer Cell Granule Protein (NKG7) promotes the development of vaccine-induced anti-fungal Th1 cells

CD4+ T cells that produce IFN-{gamma} (T helper 1 [Th1] cells) chiefly mediate vaccine acquired resistance to fungal infections. However, the key regulators of the development of Th1 cells and acquired resistance to fungi are incompletely understood. Here, we report that Natural Killer Cell Granule Protein (NKG7) acts as an unappreciated regulator inducing anti-fungal Th1 cells to produce IFN-{gamma} and converting plastic Th17 cells into polyfunctional memory Th1 cells. Author summaryThe mechanisms of vaccine resistance to fungi are incompletely understood. We identified a regulator that promotes the development of proinflammatory immune lymphocytes and fosters the conversion of one population of lymphocytes into multi-functional cells that produce several proinflammatory soluble factors that efficiently combat infectious diseases.

immunology↗

bioRxiv2026

Homotypic SLAMF1:SLAMF1 interactions between innate T cells and neutrophils activate fungal killing by neutrophils

Neutrophils and monocytes are the main fungal effector cells in restricting Blastomyces dermatitidis (Bd) and other fungi at the respiratory mucosa. However, understanding how phagocytes become activated and recruited to the site of infection is still incompletely understood. Innate lymphocytes and myeloid cells have been found to communicate and play an essential part in activating neutrophils and other effector cells to kill fungi. Here, we identified that Signaling Lymphocytic Activation Molecule 1 (SLAMF1) is a key host immune receptor involved in orchestrating a cellular and molecular signaling network that leads to the activation of phagocytes. By using mice to conditionally eliminate SLAMF1 receptor expression on innate CD4+ or TCR{gamma}{delta}+ T cells, we uncovered that these innate lymphocytes augment neutrophil killing of Bd in a SLAMF1 dependent manner. SLAMF1 expression on neutrophils enabled homotypic SLAMF1:SLAMF1 interactions with innate CD4+ T cells, which prompted release of soluble factors that activated neutrophils to kill fungi. Our work furnishes new mechanistic insight about the role of SLAMF1 in mobilizing innate immune cells to induce phagocyte-driven killing of inhaled fungi. Author SummaryEmerging fungal diseases represent a significant and growing global public health threat fueled by increased anti-fungal resistance and rising number of immunocompromised individuals. Most fungal infections are respiratory and occur when inhaled fungal spores settle in the lungs and cause inflammation or tissue damage. The innate immune system is the first line of defense in the lungs but the mechanisms by which the host immune system becomes activated and mounts a protective response is still not completely understood. We identified a receptor on innate immune cells that facilitates communication between cells and recruits and activates killer cells that engulf and destroy the fungal pathogen. We uncovered that the receptor on the cell surface of innate immune cells mediates its function through cell contact and induction of soluble factors. Our work offers new mechanistic insight about how the innate immune system becomes activated by the presence of fungi and orchestrates an effective host response. We envision that soluble receptor could be harnessed for future anti-fungal therapy.

immunology↗

bioRxiv2020

Actin-binding compounds, discovered by FRET-based high-throughput screening, differentially affect skeletal and cardiac muscle

We have used spectroscopic and functional assays to evaluate the effects of a group of actin-binding compounds on striated muscle protein structure and function. Actin is present in every human cell, and its interaction with multiple myosin isoforms and multiple actin-binding proteins is essential for cellular viability. A previous high-throughput time-resolved fluorescence resonance energy transfer (TR-FRET) assay from our group identified a class of compounds that bind to actin and affect actomyosin structure and function. In the current study, we tested their effects on the two isoforms of striated muscle -actins, skeletal and cardiac. We found that a majority of these compounds affected the transition of monomeric G-actin to filamentous F-actin, and that these effects were different for the two actin isoforms, suggesting a different mode of action. To determine the effects of these compounds on sarcomeric function, we further tested their activity on skeletal and cardiac myofibrils. We found that several compounds affected ATPase activity of skeletal and cardiac myofibrils differently, suggesting different mechanisms of action of these compounds for the two muscle types. We conclude that these structural and biochemical assays can be used to identify actin-binding compounds that differentially affect skeletal and cardiac muscles. The results of this study set the stage for screening of large chemical libraries for discovery of novel compounds that act therapeutically and specifically on cardiac or skeletal muscle.

biophysics↗