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Updated: Feb 28, 2026
Live Imaging of Antifungal Activity by Human Primary Neutrophils and Monocytes in Response to A. fumigatus
Published on: April 19, 2017
Homotypic SLAMF1:SLAMF1 interactions between innate T cells and neutrophils activate fungal killing by neutrophils
Lindsay S Lau1, Sarah Lichtenberger1, Cleison Ledesma Taira1
1Department of Pediatrics, Immunology University of Wisconsin & Infectious Diseases, Madison, WI, USA.
Abstract:
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 TCRγδ+ 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.
Insights
Signaling Lymphocytic Activation Molecule 1 (SLAMF1) is crucial for activating immune cells to fight fungal infections. This receptor on innate lymphocytes enhances neutrophil antifungal activity through cell-to-cell contact and soluble factors.
Area of Science:
- Immunology
- Infectious Diseases
- Cell Biology
Background:
- Fungal infections, particularly respiratory ones, pose a growing public health threat due to increasing antifungal resistance and immunocompromised populations.
- The innate immune system's response to inhaled fungi is not fully understood, hindering the development of effective treatments.
- Neutrophils and monocytes are key effector cells against fungi, but their activation and recruitment mechanisms require further elucidation.
Purpose of the Study:
- To identify host immune receptors involved in orchestrating phagocyte activation and recruitment against fungal pathogens.
- To elucidate the role of Signaling Lymphocytic Activation Molecule 1 (SLAMF1) in the innate immune response to fungal infections.
- To understand the cellular and molecular mechanisms by which innate lymphocytes enhance phagocyte-mediated fungal killing.
Main Methods:
- Conditional elimination of SLAMF1 receptor expression on specific innate immune cell populations (CD4+ T cells, TCRγδ+ T cells) in mice.
- Analysis of SLAMF1-dependent interactions between innate lymphocytes and neutrophils.
- Assessment of neutrophil activation and fungal killing capacity following SLAMF1 engagement.
Main Results:
- SLAMF1 is identified as a key host immune receptor mediating communication and activation of phagocytes against fungi.
- SLAMF1 expression on innate CD4+ and TCRγδ+ T cells augments neutrophil killing of Blastomyces dermatitidis (Bd) in a SLAMF1-dependent manner.
- SLAMF1:SLAMF1 homotypic interactions between neutrophils and innate CD4+ T cells trigger the release of soluble factors that activate neutrophils for enhanced fungal killing.
Conclusions:
- SLAMF1 plays a critical role in mobilizing innate immune cells to combat inhaled fungal infections.
- SLAMF1 facilitates intercellular communication, leading to enhanced phagocyte-driven fungal clearance.
- Targeting SLAMF1 or its signaling pathways presents a potential therapeutic strategy for fungal diseases.
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