Abstract
Mucormycosis is an invasive fungal infection characterised by rapid filamentous growth, which leads to angioinvasion, thrombosis, and tissue necrosis. The high mortality rates (50–100%) associated with mucormycosis are reflective of not only the aggressive nature of the infection and the poor therapeutics currently employed, but also the failure of the human immune system to successfully clear the 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 in vitro. Dendritic cells are activated in response to Mucorales hyphae only, and induce adaptive immunity. It is crucial to further knowledge regarding our immune system’s failure to eradicate resting spores under intact immunity and inhibit fungal growth under immunocompromised conditions, in order to understand mucormycosis pathogenicity and enhance therapeutic strategies for mucormycosis.
Highlights
There has been a stark increase in invasive fungal infections over the past two decades [1].One such infection is mucormycosis, which is caused by species of the Mucorales order
Platelets adhere to both mucormycete spores and hyphae, and exhibit germination suppression and hyphal damage capacity in vitro
Natural killer (NK) cell activity is highly dependent upon signalling from macrophages, dendritic cells (DC), and T cells [50]
Summary
There has been a stark increase in invasive fungal infections over the past two decades [1] One such infection is mucormycosis, which is caused by species of the Mucorales order. Rhizopus oryzae is the most common causative agent of mucormycosis, followed by Mucor circinelloides and Lichtheimia corymbifera, which collectively account for around 70% of infections [2,3,4,5,6]. This life-threatening invasive fungal infection carries an extortionate mortality rate, which is estimated at >95% in those with disseminated disease [7]. Fungi 2017, 3, 48 the Mucorales interaction with the host, in prospect of identifying novel drug targets or treatment strategies [10]
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