CAWS administration increases the expression of interferon γ and complement factors that lead to severe vasculitis in DBA/2 mice.
BACKGROUND
Candida albicans water-soluble fraction (CAWS), a mannoprotein-β-glucan complex obtained from the culture supernatant of C. albicans NBRC1385, causes CAWS-mediated vasculitis (CAWS-vasculitis) in B6 and DBA/2 mice with mild and lethal symptoms, respectively. Why CAWS is lethal only in DBA/2 mice remains unknown.


RESULTS
We performed DNA microarray analyses using mRNA obtained from peripheral blood mononuclear cells (PBMCs) of B6 and DBA/2 mice and compared their respective transcriptomes. We found that the mRNA levels of interferon-γ (Ifng) and several genes that regulate the complement system, such as C3, C4, Cfb, Cfh, and Fcna, were increased dramatically only in DBA/2 mice at 4 and 8 weeks after CAWS administration. The dramatic increase was confirmed by quantitative real-time polymerase chain reactions (qRT-PCR). Moreover, mRNA levels of immune-related genes, such as Irf1, Irf7, Irf9, Cebpb, Ccl4, Itgam, Icam1, and IL-12rb1, whose expression levels are known to be increased by Ifng, were also increased, but only in DBA/2 mice. By contrast, the mRNA level of Dectin-2, the critical receptor for the α-mannans of CAWS, was increased slightly and similarly in both B6 and DBA/2 mice after CAWS administration.


CONCLUSIONS
Taken together, our results suggest that CAWS administration induces Dectin-2 mediated CAWS-vasculitis in both B6 and DBA/2 mice and the expression of Ifng, but only in DBA/2 mice, which led to increased expression of C3, C4, Cfb, Cfh, and Fcna and an associated increase in lethality in these mice. This model may contribute to our understanding of the pathogenesis of severe human vasculitis.
Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0329, Japan. ohnonao@toyaku.ac.jp.
Noriko
N
Nagi-Miura
Daisuke
D
Okuzaki
Kosuke
K
Torigata
Minami A
MA
Sakurai
Akihiko
A
Ito
Naohito
N
Ohno
Hiroshi
H
Nojima
D000818:Animals; D002176:Candida albicans / Q000737:chemistry / Q000276:immunology*; D016000:Cluster Analysis; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology*; D053263:Gene Regulatory Networks / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D012995:Solubility; D059467:Transcriptome / Q000235:genetics / Q000276:immunology*; D014657:Vasculitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D014867:Water / Q000737:chemistry; D047071:beta-Glucans / Q000276:immunology
D008562:Membrane Glycoproteins; D047071:beta-Glucans; C025363:mannoproteins; D014867:Water; D007371:Interferon-gamma; D003165:Complement System Proteins