Different types of fungal DNA trigger different immune responses in the body. DNA from the common yeast Candida albicans promotes immune tolerance and protects T cells, similar to beneficial bacterial DNA. In contrast, DNA from the pathogenic fungus Cryptococcus neoformans triggers strong inflammatory immune responses. This discovery reveals that fungal DNA itself, not just fungal cell wall components, plays an important role in determining whether fungi are treated as friendly commensals or dangerous pathogens by the immune system.