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Inherited IL-17RC deficiency in patients with chronic mucocutaneous candidiasis.

Ling Y, Cypowyj S, Aytekin C, Galicchio M, Camcioglu Y, Nepesov S, Ikinciogullari A, Dogu F, Belkadi A, Levy R, Migaud M, Boisson B, Bolze A, Itan Y, Goudin N, Cottineau J, Picard C, Abel L, Bustamante J, Casanova JL, Puel A - J. Exp. Med. (2015)

Bottom Line: The defect is complete, abolishing cellular responses to IL-17A and IL-17F homo- and heterodimers.However, in contrast to what is observed for the IL-17RA- and ACT1-deficient patients tested, the response to IL-17E (IL-25) is maintained in these IL-17RC-deficient patients.These experiments of nature indicate that human IL-17RC is essential for mucocutaneous immunity to C. albicans but is otherwise largely redundant.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163, 75015 Paris, France Imagine Institute, Paris Descartes University, 75015 Paris, France.

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Normal TNF production by P2’s and P3′s MDDCs upon 48 h of stimulation with fungal compounds. (A and B) MDDCs from four healthy control individuals (white bars), four heterozygous patients’ relatives (gray bars), and P2 or P3 (black bars) were stimulated with fungal compounds (zymosan, heat-killed S. cerevisiae [HKSC], C. albicans [HKCA and SC5314], E. dermatitidis, and Curdlan), as well as with VSV, BCG, or LPS for 48 h. TNF was measured by ELISA. Error bars represent SEM. The experiments were repeated two times.
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fig10: Normal TNF production by P2’s and P3′s MDDCs upon 48 h of stimulation with fungal compounds. (A and B) MDDCs from four healthy control individuals (white bars), four heterozygous patients’ relatives (gray bars), and P2 or P3 (black bars) were stimulated with fungal compounds (zymosan, heat-killed S. cerevisiae [HKSC], C. albicans [HKCA and SC5314], E. dermatitidis, and Curdlan), as well as with VSV, BCG, or LPS for 48 h. TNF was measured by ELISA. Error bars represent SEM. The experiments were repeated two times.

Mentions: Finally, we investigated IL-6, IFN-γ, and IL-17A production by P2’s whole blood upon 48 h of stimulation with fungal compounds (Curdlan, heat-killed C. albicans, Saccharomyces cerevisiae, and Exophiala dermatitidis), as well as heat-killed Staphylococcus aureus, vesicular stomatitis virus (VSV), bacillus Calmette–Guérin (BCG), and PMA/ionomycin. The levels of all three cytokines produced were comparable with those obtained after whole blood stimulation of a local or a travel control (Fig. 9, A–C). Similarly, monocyte-derived DCs (MDDCs) from P2, P3, and their relatives, activated with various fungal compounds (including zymosan, heat-killed S. cerevisiae, C. albicans, E. dermatitidis, and Curdlan), as well as VSV, BCG, or LPS, produced levels of TNF comparable with the healthy controls tested in the same conditions (Fig. 10, A and B). Altogether, these results suggest that IL-17RC deficiency does not impair the whole blood or MDDC response to fungal compounds, at least for the cytokines measured, including IL-17A. Altogether, these data suggest that the patients’ defective IL-17RC–dependent responsive pathway is primarily responsible for CMC, as it does not affect the production of IL-17A and other cytokines by leukocytes and MDDCs in response to stimulation by C. albicans.


Inherited IL-17RC deficiency in patients with chronic mucocutaneous candidiasis.

Ling Y, Cypowyj S, Aytekin C, Galicchio M, Camcioglu Y, Nepesov S, Ikinciogullari A, Dogu F, Belkadi A, Levy R, Migaud M, Boisson B, Bolze A, Itan Y, Goudin N, Cottineau J, Picard C, Abel L, Bustamante J, Casanova JL, Puel A - J. Exp. Med. (2015)

Normal TNF production by P2’s and P3′s MDDCs upon 48 h of stimulation with fungal compounds. (A and B) MDDCs from four healthy control individuals (white bars), four heterozygous patients’ relatives (gray bars), and P2 or P3 (black bars) were stimulated with fungal compounds (zymosan, heat-killed S. cerevisiae [HKSC], C. albicans [HKCA and SC5314], E. dermatitidis, and Curdlan), as well as with VSV, BCG, or LPS for 48 h. TNF was measured by ELISA. Error bars represent SEM. The experiments were repeated two times.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4419340&req=5

fig10: Normal TNF production by P2’s and P3′s MDDCs upon 48 h of stimulation with fungal compounds. (A and B) MDDCs from four healthy control individuals (white bars), four heterozygous patients’ relatives (gray bars), and P2 or P3 (black bars) were stimulated with fungal compounds (zymosan, heat-killed S. cerevisiae [HKSC], C. albicans [HKCA and SC5314], E. dermatitidis, and Curdlan), as well as with VSV, BCG, or LPS for 48 h. TNF was measured by ELISA. Error bars represent SEM. The experiments were repeated two times.
Mentions: Finally, we investigated IL-6, IFN-γ, and IL-17A production by P2’s whole blood upon 48 h of stimulation with fungal compounds (Curdlan, heat-killed C. albicans, Saccharomyces cerevisiae, and Exophiala dermatitidis), as well as heat-killed Staphylococcus aureus, vesicular stomatitis virus (VSV), bacillus Calmette–Guérin (BCG), and PMA/ionomycin. The levels of all three cytokines produced were comparable with those obtained after whole blood stimulation of a local or a travel control (Fig. 9, A–C). Similarly, monocyte-derived DCs (MDDCs) from P2, P3, and their relatives, activated with various fungal compounds (including zymosan, heat-killed S. cerevisiae, C. albicans, E. dermatitidis, and Curdlan), as well as VSV, BCG, or LPS, produced levels of TNF comparable with the healthy controls tested in the same conditions (Fig. 10, A and B). Altogether, these results suggest that IL-17RC deficiency does not impair the whole blood or MDDC response to fungal compounds, at least for the cytokines measured, including IL-17A. Altogether, these data suggest that the patients’ defective IL-17RC–dependent responsive pathway is primarily responsible for CMC, as it does not affect the production of IL-17A and other cytokines by leukocytes and MDDCs in response to stimulation by C. albicans.

Bottom Line: The defect is complete, abolishing cellular responses to IL-17A and IL-17F homo- and heterodimers.However, in contrast to what is observed for the IL-17RA- and ACT1-deficient patients tested, the response to IL-17E (IL-25) is maintained in these IL-17RC-deficient patients.These experiments of nature indicate that human IL-17RC is essential for mucocutaneous immunity to C. albicans but is otherwise largely redundant.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163, 75015 Paris, France Imagine Institute, Paris Descartes University, 75015 Paris, France.

Show MeSH
Related in: MedlinePlus