Homotypic interactions between SLAMF1 receptors on innate T cells and neutrophils regulate killing of fungi.

Innate lymphocytes and myeloid cells 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) orchestrates a cellular and molecular signaling network that activates phagocytes. We uncovered innate lymphocytes including innate CD4+ or TCRγδ+ T cells augment neutrophil killing of Blastomyces dermatitidis (Bd) in a SLAMF1 dependent manner. SLAMF1 expression on neutrophils enabled homotypic SLAMF1:SLAMF1 interactions with innate CD4+ T cells, which released 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.