Innate and adaptive immunity to Mucorales

Mucormycosis is an invasive fungal infection characterised by rapid filamentous growth leading to angioinvasion, thrombosis and tissue necrosis. The high mortality rates (50-100%) associated with mucormycosis are reflective not only of the aggressive nature of the infection and the poor therapeutics currently employed, but also the failure of the human immune system to successfully clear infection. Immune effector interaction with Mucorales is influenced by the developmental stage of the mucormycete spore. In a healthy immune environment, resting spores are resistant to phagocytic killing. Contrarily, swollen spores and hyphae are susceptible to damage and degradation by macrophages and neutrophils. Under the effects of immune suppression, the recruitment and efficacy of macrophage and neutrophil activity against mucormycetes is considerably reduced. Following penetration of the endothelial lining, Mucorales encounter platelets. Platelets adhere to both mucormycete spores and hyphae and exhibit germination suppression and hyphal damage capacity. Dendritic cells are activated in response to Mucorales hyphae only, inducing adaptive immunity. Furthering our knowledge of our immune system’s failure to eradicate resting spores under intact immunity and to inhibit fungal growth under immunocompromised conditions is crucial in understanding mucormycosis pathogenicity and for the enhancement of therapeutic strategies for mucormycosis.