Coronary Vasculitis Induced in Mice by the Cell Wall Mannoprotein of <i>Candida krusei</i>

Abstract

Kawasaki disease (KD) is an inflammatory disease that was identified by Professor Tomisaku Kawasaki in 1961. Candida albicans-derived substances, such as the hot water extract of C. albicans (CADS) and Candida water-soluble fraction (CAWS), induced coronary vasculitis similar to KD in mice. An increasing proportion of deep-seated candidiasis cases are caused by non-albicans Candida and are often resistant to antifungal drugs. We herein investigated whether the hot water extract of C. krusei, inherently resistant to fluconazole, induces vasculitis in mice. Three strains of C. krusei, NBRC1395, NBRC1162, and NBRC10737, were cultured in natural (Y) and chemically defined (C) media and cell wall mannoprotein (MN) fractions were prepared by autoclaving cells (CKY1395MN, CKC1395MN, CKY1162MN, CKC1162MN, CKY10737MN, and CKC10737MN). All MN fractions reacted strongly with Con A and dectin-2 and induced anaphylactoid shock in ICR mice. MNs induced severe coronary vasculitis in DBA/2 mice, resulting in cardiac hypertrophy. MNs also induced coronary vasculitis in C57Bl/6 mice. These results suggest that the MNs of non-albicans Candida, such as C. krusei, induce similar toxicity to those of C. albicans.

Coronary Vasculitis Induced in Mice by Cell Wall Mannoprotein Fractions of Clinically Isolated <i>Candida</i> Species

“…We demonstrated that the vasculitis activity of CAWS negatively corelated with the presence of β-mannose residues 11,12) . We also confirmed that coronary vasculitis was induced by the hot water extract (HWE) of the standard strains of Candida albicans, Candida metapsilosis, and Candida krusei [13][14][15][16] . Chemical and NMR spectral analyses strongly suggested that the major polysaccharide component of HWE is the cell wall mannan, thus the vasculitis activity might be strongly related to the presence and the structure of mannan moiety [13][14][15][16] .…”

“…We also confirmed that coronary vasculitis was induced by the hot water extract (HWE) of the standard strains of Candida albicans, Candida metapsilosis, and Candida krusei [13][14][15][16] . Chemical and NMR spectral analyses strongly suggested that the major polysaccharide component of HWE is the cell wall mannan, thus the vasculitis activity might be strongly related to the presence and the structure of mannan moiety [13][14][15][16] . CAWS-vasculitis, particularly in DBA/2 mice, is severe and ultimately results in death due to cardiac hypertrophy 12,17,18) .…”

“…CAWS-vasculitis, particularly in DBA/2 mice, is severe and ultimately results in death due to cardiac hypertrophy 12,17,18) . Vasculitis is induced not only by the MN fractions of the standard strains of C. albicans, but also by those of C. metapsilosis and C. krusei 13,15,16) . Knockout mice for Dectin-2, a PRR for fungal pathogens, are resistant to CAWS-vasculitis, suggesting that the activation of dectin-2 signaling by MN fractions is one of the key steps in the induction of vasculitis 52) .…”

“…Two clinically isolated strains, C. albicans KYUP#3 and C. krusei KYUP#35, were used to set up the experimental protocol to analyze vasculitis-inducing activity. These strains were cultured for 2 days using natural (YPD medium) and chemically defined (C-limiting medium) media, and the crude cell wall mannoprotein fractions (MN fraction) were prepared using hot water extraction, in accordance with the method used for standard strains 13,15,16) . The resulting MN fractions were abbreviated as CAC3 (C. albicans C-limit #3), CAY3 (C. albicans YPD#3), CKC35, and CKY35, respectively.…”

“…To investigate these topics, we attempted to prepare the extracellular MN fractions (CAWS-like molecules) from several Candida strains; however, the yield of the extracellular fractions significantly differed in a strain-dependent manner (data not shown). In addition, we have prepared the cell wall MN fractions from C. albicans NBRC1385 and have demonstrated the similarities in vasculitis and anaphylactoid shock induced by these fractions and by CAWS 14,16) . In the present study, we prepared MN fractions from clinically isolated Candida species and examined coronary vasculitis induced by these fractions.…”