Advances in cryptococcal infections-associated immunopathology and potential therapeutic strategies

Globally, the Cryptococcus species, particularly Cryptococcus neoformans and Cryptococcus gattii, have a significant impact on human health. Concurrent with the evolving epidemiology of cryptococcosis, it has now become evident how host immunity contributes to the pathophysiology of severe disease. The only pharmacological antifungal therapeutic agents available are 5-flucytosine, fluconazole, and amphotericin B. Echinocandins, the newest fungicidal class for invasive mycoses, are ineffective against cryptococcosis caused by C. neoformans. Antifungal treatment is hampered by the high toxicity, elevated resistance rate, and difficulty of currently known antifungal compounds crossing the blood-brain barrier, in addition to the limited pharmaceutical choices. Therefore, it is imperative to find novel therapeutic options for cryptococcal infections. This article will summarize what is now understood about the immunopathology linked to cryptococcal infections that produce a tolerant phenotype. We also outline the current possible antifungal therapeutic approaches to control cryptococcal illness. We go into further detail on the most recent developments in our knowledge of the adaptive and intrinsic resistance mechanisms used by Cryptococcus species to avoid medical interventions. Together with developments in genomics technology and high-throughput screening techniques, knowledge of the processes governing anti-cryptococcal drug resistance will, in general, spur innovation and quicken the discovery of antifungal drugs.