Cell wall mannan of Candida krusei mediates dendritic cell apoptosis and orchestrates Th17 polarization via TLR-2/MyD88-dependent pathway

被引:19
作者
Thu Ngoc Yen Nguyen [1 ]
Padungros, Panuwat [2 ]
Wongsrisupphakul, Panachai [2 ]
Sa-Ard-Iam, Noppadol [3 ]
Mahanonda, Rangsini [3 ,4 ]
Matangkasombut, Oranart [5 ,6 ,7 ]
Choo, Min-Kyung [8 ,9 ]
Ritprajak, Patcharee [6 ,7 ,10 ]
机构
[1] Chulalongkorn Univ, Grad Program Oral Biol, Fac Dent, Bangkok 10330, Thailand
[2] Chulalongkorn Univ, Fac Sci, Dept Chem, Organ Synth Res Unit, Phayathai Rd, Bangkok 10330, Thailand
[3] Chulalongkorn Univ, Immunol Lab, Fac Dent, Bangkok 10330, Thailand
[4] Chulalongkorn Univ, Dept Periodontol, Fac Dent, Bangkok 10330, Thailand
[5] Chulabhorn Res Inst, Biotechnol Lab, Bangkok 10210, Thailand
[6] Chulalongkorn Univ, Fac Dent, Res Unit Oral Microbiol & Immunol, Bangkok 10330, Thailand
[7] Chulalongkorn Univ, Fac Dent, Dept Microbiol, Bangkok 10330, Thailand
[8] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA
[9] Harvard Med Sch, Charlestown, MA 02129 USA
[10] Chulalongkorn Univ, Oral Biol Res Ctr, Fac Dent, Bangkok, Thailand
来源
SCIENTIFIC REPORTS | 2018年 / 8卷
关键词
PATTERN-RECOGNITION RECEPTOR; HOST-DEFENSE; IFN-GAMMA; BETA-1,2-LINKED OLIGOMANNOSIDES; ALBICANS PHOSPHOLIPOMANNAN; ECHINOCANDIN RESISTANCE; PATHOGENIC YEAST; INTERFERON-GAMMA; TYROSINE KINASE; SYK;
D O I
10.1038/s41598-018-35101-3
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Dendritic cells (DCs) abundantly express diverse receptors to recognize mannans in the outer surface of Candida cell wall, and these interactions dictate the host immune responses that determine disease outcomes. C. krusei prevalence in candidiasis worldwide has increased since this pathogen has developed multidrug resistance. However, little is known how the immune system responds to C. krusei. Particularly, the molecular mechanisms of the interplay between C. krusei mannan and DCs remain to be elucidated. We investigated how C. krusei mannan affected DC responses in comparison to C. albicans C. tropicalis and C. glabrata mannan. Our results showed that only C. krusei mannan induced massive cytokine responses in DCs and led to apoptosis. Although C. krusei mannan-activated DCs underwent apoptosis, they were still capable of initiating Th17 response. C. krusei mannan-mediated DC apoptosis was obligated to the TLR2 and MyD88 pathway. These pathways also controlled Th1/Th17 switching possibly by virtue of the production of the polarizing cytokines IL-12 and IL-6 by the C. krusei mannan activated-DCs. Our study suggests that TLR2 and MyD88 pathway in DCs are dominant for C. krusei mannan recognition, which differs from the previous reports showing a crucial role of C-type lectin receptors in Candida mannan sensing.
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页数:16
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