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Immune Sensing of Aspergillus fumigatus Proteins, Glycolipids, and Polysaccharides and the Impact on Th Immunity and Vaccination¹

Silvia Bozza^*, Cecile Clavaud, Gloria Giovannini^*, Thierry Fontaine, Anne Beauvais, Jacqueline Sarfati, Carmen D'Angelo^*, Katia Perruccio^*, Pierluigi Bonifazi^*, Silvia Zagarella^*, Silvia Moretti^*, Francesco Bistoni^*, Jean-Paul Latgé and Luigina Romani^2,*

^* Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy; and Unite des Aspergillus, Institut Pasteur, Paris, France

The ability of the fungus Aspergillus fumigatus to activate, suppress, or subvert host immune response during life cycle in vivo through dynamic changing of cell wall structure and secretion implicates discriminative immune sensing of distinct fungal components. In this study, we have comparatively assessed secreted- and membrane-anchored proteins, glycolipids, and polysaccharides for the ability to induce vaccine-dependent protection in transplanted mice and Th cytokine production by human-specific CD4⁺ T cell clones. The results show that the different fungal components are endowed with the distinct capacity to activate Th cell responses in mice and humans, with secreted proteins inducing Th2 cell activation, membrane proteins Th1/Treg, glycolipids Th17, and polysaccharides mostly IL-10 production. Of interest, the side-by-side comparison revealed that at least three fungal components (a protease and two glycosylphosphatidylinositol-anchored proteins) retained their immunodominant Th1/Treg activating potential from mice to humans. This suggests that the broadness and specificity of human T cell repertoire against the fungus could be selectively exploited with defined immunoactive Aspergillus Ags.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by the Specific Targeted Research Project MANASP (LSHE-CT-2006), contract number 037899 (FP6) (to L.R. and J.P.L.) and the Italian Projects PRIN 2007KLCKP8_004 (to L.R.), 2007XYB9T9_001 (to S.B.), and 2007KLCKP8_005 (to F.B.).

² Address correspondence and reprint requests to Dr. Luigina Romani, Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06126 Perugia, Italy. E-mail address: lromani{at}unipg.it

³ Abbreviations used in this paper: Treg, regulatory T cell; BAL, broncho-alveolar lavage fluid; Cat1p, mycelia catalase 1; Crf1p, β1,6 glucan-chitin linkages; DC, dendritic cell; Gel1p, 1,3-β glucanosyltransferase; GM, galactomannan; GPI, glycosylphosphatidylinositol; GSL, glycosylinositolphosphoceramide; LGM, GPI-anchored lipophosphogalactomannan; Pep1p, aspartic protease; Sod1p, Superoxide dismutase; TLN, thoracic lymph nodes.