Journal Article

Immune response to Candida albicans is preserved despite defect in O-mannosylation of secretory proteins

Cristina Corbucci, Elio Cenci, Franck Skrzypek, Elena Gabrielli, Paolo Mosci, Joachim F. Ernst, Francesco Bistoni and Anna Vecchiarelli

in Medical Mycology

Published on behalf of International Society for Human and Animal Mycology

Volume 45, issue 8, pages 709-719
Published in print December 2007 | ISSN: 1369-3786
Published online December 2007 | e-ISSN: 1460-2709 | DOI: https://dx.doi.org/10.1080/13693780701537922
Immune response to Candida albicans is preserved despite defect in O-mannosylation of secretory proteins

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  • Mycology and Fungi
  • Infectious Diseases
  • Medical Toxicology
  • Veterinary Medicine
  • Environmental Science

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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-κB 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.

Keywords: C. albicans; TLR; innate immunity; macrophages; fungi

Journal Article.  4942 words.  Illustrated.

Subjects: Mycology and Fungi ; Infectious Diseases ; Medical Toxicology ; Veterinary Medicine ; Environmental Science

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