CARD9 Is Required for Classical Macrophage Activation and the Induction of Protective Immunity against Pulmonary Cryptococcosis

TLDR

Cryptococcus neoformans is a ubiquitous fungal pathogen that can cause life‑threatening lung and CNS infections in immunocompromised individuals, and CARD9—a key molecule activated by C‑type lectin receptor interactions with fungal carbohydrates—is essential for host defense, as CARD9 deficiency increases susceptibility to many fungal infections. The study aimed to determine whether CARD9 is required for protective immunity against C. neoformans infection. The authors evaluated CARD9’s role by assessing its necessity in the induction of protective immunity against C.

Abstract

Cryptococcus neoformans is a fungal pathogen that is found throughout the environment and can cause life-threatening infections of the lung and central nervous system in severely immunocompromised individuals. Caspase recruitment domain-containing protein 9 (CARD9) is a critical molecule that is activated after interactions of C-type lectin receptors (CLRs) found on the surfaces of specific immune cells, with carbohydrate structures associated with fungi. Patients with defects in CARD9 are significantly more susceptible to a multitude of fungal infections. C. neoformans contains several carbohydrate structures that interact with CLRs on immune cells and activate CARD9. Consequently, these studies evaluated the necessity of CARD9 for the induction of protective immunity against C. neoformans infection. These results are important, as they advance our understanding of cryptococcal pathogenesis and host factors necessary for the induction of protective immunity against C. neoformans .