Immune response to Candida albicans is preserved despite defect in O-mannosylation of secretory proteins.
The PMT gene family in Candida albicans encodes five isoforms of the protein mannosyltransferases that initiate O-mannosylation of secretory proteins. Mutations at the Pmt level have been associated with differences in pathogenicity, e.g. in contrast to pmt5/pmt5, pmt2/PMT2 mutants showed poor virulence. Our objective was to determine whether these differences were related to the capacity of pmt2/PMT2 and pmt5/pmt5 to (i) express differences in selected virulence factors, and (ii) stimulate the natural immune system. The results show that pmt mutants (i) form hyphae in serum, (ii) show defective production of proteases but not of phospholipases with respect to the parental strain, (iii) undergo mycelial transition in the kidneys of hematogenously infected animals, (iv) are phagocytosed and killed by macrophages similar to the parental strain, although neutrophils are unable to destroy pmt5/pmt5, (v) engage TLR4 and stimulate MyD88 leading to NF-kappaB activation, and (vi) stimulate cytokine production by macrophages. Collectively our findings suggest that the defect in protein O-mannosylation in C. albicans cause attenuation of the virulence although the antigenic factors that retain the capacity to stimulate an efficient immune response are preserved.
Corbucci
Cristina
C
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Cenci
Elio
E
Skrzypek
Franck
F
Gabrielli
Elena
E
Mosci
Paolo
P
Ernst
Joachim F
JF
Bistoni
Francesco
F
Vecchiarelli
Anna
A
D000818:Animals; D015153:Blotting, Western; D002176:Candida albicans / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D002177:Candidiasis / Q000276:immunology*; D005260:Female; D006651:Histocytochemistry; D007113:Immunity, Innate / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D007668:Kidney / Q000382:microbiology; D017737:Macrophages, Peritoneal / Q000276:immunology; D008364:Mannosyltransferases / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009154:Mutation / Q000276:immunology; D010447:Peptide Hydrolases / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D010740:Phospholipases / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D014774:Virulence
C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D018664:Interleukin-12; D008364:Mannosyltransferases; D010740:Phospholipases; D010447:Peptide Hydrolases