The roles of fungus in CNS autoimmune and neurodegeneration disorders

Abstract

Fungal infection or proliferation in our body is capable of initiation of strong inflammation and immune responses that result in different consequences, including infection-trigged organ injury and inflammation-related remote organ dysfunction. Fungi associated infectious diseases have been well recognized in the clinic. However, whether fungi play an important role in non-infectious central nervous system disease is still to be elucidated. Recently, a growing amount of evidence point to a non-negligible role of peripheral fungus in triggering unique inflammation, immune response, and exacerbation of a range of non-infectious CNS disorders, including Multiple sclerosis, Neuromyelitis optica, Parkinson’s disease, Alzheimer’s disease, and Amyotrophic lateral sclerosis et al. In this review, we summarized the recent advances in recognizing patterns and inflammatory signaling of fungi in different subsets of immune cells, with a specific focus on its function in CNS autoimmune and neurodegeneration diseases. In conclusion, the fungus is capable of triggering unique inflammation by multiple mechanisms in the progression of a body of CNS non-infectious diseases, suggesting it serves as a key factor and critical novel target for the development of potential therapeutic strategies.

Retrovirus-Derived RTL9 Plays an Important Role in Innate Antifungal Immunity in the Eutherian Brain

“…RTL9 is a promising antifungal therapy target as a newly identified member of innate antifungal immunity in eutherians. Furthermore, fungal infections in patients with Alzheimer's disease (AD) have been reported [40][41][42], suggesting that fungal infection may also be involved in the etiology of AD and/or other neurodegenerative diseases and non-infectious autoimmune diseases, such as multiple sclerosis, neuromyelitis optica, amyotropic lateral sclerosis and Parkinson's disease [40][41][42][43][44][45][46][47]. Recent studies on innate and adaptive immunity have reported that phagocytic cells are essential players in protecting against fungal diseases and that defects in these cells compromise the host's ability to resist fungal infection [30,31].…”

The Role of Microorganisms in the Etiopathogenesis of Demyelinating Diseases

“…Recent studies have shown that fungi may play an important role in the pathogenesis of MS [ 14 ] and the finding that genes involved in innate immunity are associated with the disease suggests a link between MS and dysregulation of the innate immune system [ 18 ].…”

“…Fungal toxins could have a direct role in the development of the disease by damaging oligodendrocytes and astrocytes, but the peripheral action of fungi on the immune system may also make a contribution [ 14 , 133 ].…”

“…Even if viruses are considered as the microorganisms that are more implicated in the pathogenesis of demyelinating diseases, it has recently been suggested that fungi also play a role. Considering that CD4+ T cells are indispensable to protecting the organism against fungal infections, an overactivation of these immune cells could potentially lead to autoimmunity [ 14 ].…”

Neuromicrobiology of Neurodegenerative Diseases:

“…Overall, the study of fungal footprints in neurological diseases has the potential to contribute to our understanding of the underlying mechanisms of these conditions and may ultimately lead to improved strategies for prevention and treatment (Forbes et al, 2019). In particular, research has focused on the role of fungal infections in promoting inflammation and the production of misfolded proteins, which can contribute to the development of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease (Wu et al, 2023).…”