Systemic Infection by Non-albicans Candida Species Affects the Development of a Murine Model of Multiple Sclerosis

Abstract

Candidiasis may affect the central nervous system (CNS), and although Candida albicans is predominant, non-albicans Candida species can also be associated with CNS infections. Some studies have suggested that Candida infections could increase the odds of multiple sclerosis (MS) development. In this context, we investigated whether systemic infection by non-albicans Candida species would affect, clinically or immunologically, the severity of experimental autoimmune encephalomyelitis (EAE), which is an animal model used to study MS. For this, a strain of C. glabrata, C. krusei, and C. parapsilosis was selected and characterized using different in vitro and in vivo models. In these analysis, all the strains exhibited the ability to form biofilms, produce proteolytic enzymes, and cause systemic infections in Galleria mellonella, with C. glabrata being the most virulent species. Next, C57BL/6 mice were infected with strains of C. glabrata, C. krusei, or C. parapsilosis, and 3 days later were immunized with myelin oligodendrocyte glycoprotein to develop EAE. Mice from EAE groups previously infected with C. glabrata and C. krusei developed more severe and more prevalent paralysis, while mice from the EAE group infected with C. parapsilosis developed a disease comparable to non-infected EAE mice. Disease aggravation by C. glabrata and C. krusei strains was concomitant to increased IL-17 and IFN-γ production by splenic cells stimulated with fungi-derived antigens and with increased percentage of T lymphocytes and myeloid cells in the CNS. Analysis of interaction with BV-2 microglial cell line also revealed differences among these strains, in which C. krusei was the strongest activator of microglia concerning the expression of MHC II and CD40 and pro-inflammatory cytokine production. Altogether, these results indicated that the three non-albicans Candida strains were similarly able to reach the CNS but distinct in terms of their effect over EAE development. Whereas C. glabrata and C. Krusei aggravated the development of EAE, C. parapsilosis did not affect its severity. Disease worsening was partially associated to virulence factors in C. glabrata and to a strong activation of microglia in C. krusei infection. In conclusion, systemic infections by non-albicans Candida strains exerted influence on the experimental autoimmune encephalomyelitis in both immunological and clinical aspects, emphasizing their possible relevance in MS development.

Mycobiome Dysbiosis in Women with Intrauterine Adhesions

“…It was unlikely to invade and damage host tissues similar to C. albicans due to its potential to protect the host from infection by C. albicans ( 50 , 51 ). Moreover, in an animal model of experimental autoimmune encephalomyelitis (EAE), it was reported that C. parapsilosis infection did not exacerbate the severity of EAE and exhibited the lowest fungal burden in the central nervous system ( 52 ). Furthermore, the yeast-hyphal morphogenesis is reported to be critical for fungal virulence ( 53 ).…”

Gellan-Based Hydrogel as a Drug Delivery System for Caffeic Acid Phenethyl Ester in the Treatment of Oral Candida albicans Infections

“…Then, the mixture was centrifuged, and the supernatant was collected and placed in 96-well UV-transparent plates. The absorbance was measured at 280 nm [ 38 ]. The sap proteolytic activity was evaluated at 2, 4, 6, 8, 10 and 12 h.…”

“…The samples were incubated for 1 h at 37 • C, and proteolytic activity was stopped by adding 5% trichloroacetic acid (TCA), followed by incubating for 1 h at 4 • C. Then, the mixture was centrifuged, and the supernatant was collected and placed in 96-well UV-transparent plates. The absorbance was measured at 280 nm [38]. The sap proteolytic activity was evaluated at 2, 4, 6, 8, 10 and 12 h.…”

The roles of fungus in CNS autoimmune and neurodegeneration disorders

“…It reported that C. albicans infection before the induction of experimental autoimmune encephalomyelitis (EAE), the classic animal model of MS, promotes the EAE onset and aggravates the disease severity ( 57 ). In addition to C. albicans , EAE was also aggravated in mice infected with non- C. albicans strains C. glabrata and C. krusei ( 58 ), suggesting a critical role of fungi in promoting EAE disease progression.…”