Immunization with a heat-killed prm1 deletion strain protects the host from <i>Cryptococcus neoformans</i> infection

Systemic infection with <i>Cryptococcus neoformans</i>, a dangerous and contagious pathogen found throughout the world, frequently results in lethal cryptococcal pneumonia and meningoencephalitis, and no effective treatments and vaccination of cryptococcosis are available. Here, we describe Prm1, a novel regulator of <i>C. neoformans</i> virulence<i>. C. neoformans prm1Δ</i> cells exhibit extreme sensitivity to various environmental stress conditions. Furthermore, <i>prm1Δ</i> cells show deficiencies in the biosynthesis of chitosan and mannoprotein, which in turn result in impairment of cell wall integrity. Treatment of mice with heat-killed <i>prm1Δ</i> cells was found to facilitate the host immunological defence against infection with wild-type <i>C. neoformans</i>. Further investigation demonstrated that <i>prm1Δ</i> cells strongly promote pulmonary production of interferon-γ, leading to activation of macrophage M1 differentiation and inhibition of M2 polarization. Therefore, our findings suggest that <i>C. neoformans</i> Prm1 may be a viable target for the development of anti-cryptococcosis medications and, cells lacking Prm1 represent a promising candidate for a vaccine.