Biology subjects

Taira, C. L.

Publications and source records attributed to Taira, C. L..

4 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

Combination adjuvants drive long lived plastic Th17 cells that convert to multi-functional Th1 cells and protect mice against fungal infection

Th1 cells are viewed as a cornerstone of immunity to fungi and other intracellular pathogens. Despite the widely accepted role of Th1 cells in antifungal resistance, the development of protective strategies harnessing them is stunted by a limited understanding of how best to promote their development. We and others have reported a requisite role for Th17 cells in resistance to fungi. We have long been puzzled about how to reconcile seminal roles for both Th1 and Th17 subsets. Here we report that Th17 cells convert into polyfunctional Th1 cells producing multiple cytokines, including IFN-{gamma}, TNF and GM-CSF when we used adjuvant formulations that include glucopyranosyl lipid adjuvant (GLA) to enhance antifungal immunity. GLA induced plastic Th17 cells that convert into polyfunctional Th1 memory cells.

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↗

bioRxiv2025

Endoglucanase-2 (Eng2), a conserved immunodominant antigen in dimorphic fungi that elicits immunity and resistance during infection

Herein, we describe a conserved surface and cell wall protein, Endoglucanase 2 (Eng2), expressed on the etiological agents that cause the endemic systemic mycoses of North America - Blastomyces, Coccidioides and Histoplasma. We demonstrate that despite sequence variation of the protein across these related fungi, exposure to Eng2 vaccinates and protects inbred and humanized HLA-DR4 strains of mice against lethal experimental infections with these fungi by eliciting adaptive immunity mediated by CD4 T cells. We also show that CD4 T cell precursors against Eng2 are detectable in naive individuals and that patients who have recovered from these infections evince a memory and recall CD4 T cell response to Eng2 and its immunodominant epitopes that we have mapped. We create and catalogue new tools and information such as immunodominant peptide epitopes of Eng2 from each fungus recognized by inbred mice and human subjects and we engineer novel peptide-MHC II tetramers for tracking T cells in inbred and HLA-DR4 humanized mice that will be useful for those who study these infections in mice and humans. Lastly, because most patients demonstrate memory and recall responses against Eng2, our work oRers new tools for diagnosis of this collection of infectious diseases across North America.

immunology↗