Multiple sclerosis and mixed microbial infections. Direct identification of fungi and bacteria in nervous tissue

• Published in: Neurobiology of disease Vol. 117; pp. 42 - 61
• Main Authors: Alonso, Ruth, Fernández-Fernández, Ana M., Pisa, Diana, Carrasco, Luis
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2018; Elsevier
• Subjects: Bacteria - isolation & purification; Bacteria and fungal co-infections; Bacterial Infections - epidemiology; Bacterial Infections - pathology; Brain - microbiology; Brain - pathology; Central Nervous System - microbiology; Central Nervous System - pathology; Coinfection - epidemiology; Coinfection - pathology; Female; Fungal infection; Fungi - isolation & purification; Humans; Male; Middle Aged; Multiple sclerosis; Multiple Sclerosis - microbiology; Multiple Sclerosis - pathology; Mycoses - epidemiology; Mycoses - pathology; Next generation sequencing; Polymicrobial infection; Sequence Analysis, DNA - methods; Spinal Cord - microbiology; Spinal Cord - pathology; Multiple sclerosis; Next generation sequencing; Polymicrobial infection; Fungal infection; Bacteria and fungal co-infections
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2018.05.022

Multiple sclerosis (MS) is the prototypical inflammatory disease of the central nervous system (CNS), leading to multifocal demyelination and neurodegeneration. The etiology of this incurable disease is unknown and remains a matter of intensive research. The possibility that microbial infections, such as viruses or bacteria, can trigger an autoimmune reaction in CNS tissue has been suggested. However, the recent demonstration that bacteria are present in CNS tissue points to a direct involvement of microbial infections in the etiology of MS. In the present study, we provide the first evidence of fungal infection in CNS tissue of MS patients, and demonstrate that fungal DNA from different species can be detected in the CNS. We used, nested PCR assays together with next-generation sequencing to identify the fungal species in the nervous tissue of 10 patients with MS. Strikingly, Trichosporon mucoides was found in the majority of MS patients, and particularly high levels of this fungus were found in two patients. Importantly, T. mucoides was not detected in the CNS of control subjects. We were also able to visualize fungal structures in CNS tissue sections by immunohistochemistry using specific antifungal antibodies, which also revealed the accumulation of a number of microbial cells in microfoci. Again, microbial structures were not observed in CNS sections from controls. In addition to fungi, neural tissue from MS patients was also positive for bacteria. In conclusion, our present observations point to the novel concept that MS could be caused by polymicrobial infections. Thus, mycosis of the CNS may be accompanied by opportunistic bacterial infection, promoting neuroinflammation and directly causing focal lesions, followed by demyelination and axonal injury. •Multiple sclerosis (MS) is the prototypical inflammatory disease of unknown etiology.•The possibility that MS is caused by microbial infections has been suggested.•We provide the first evidence that fungal infections can be detected in MS brains.•Both, fungal DNA and the direct visualization of fungal structures, can be detected.•In addition, bacteria can be identified in neural tissue from MS patients.