PMID- 30459422 OWN - NLM STAT- MEDLINE DCOM- 20191217 LR - 20240403 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 8 IP - 1 DP - 2018 Nov 20 TI - Cell wall mannan of Candida krusei mediates dendritic cell apoptosis and orchestrates Th17 polarization via TLR-2/MyD88-dependent pathway. PG - 17123 LID - 10.1038/s41598-018-35101-3 [doi] LID - 17123 AB - 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. FAU - Nguyen, Thu Ngoc Yen AU - Nguyen TNY AUID- ORCID: 0000-0003-1329-7299 AD - Graduate program in Oral Biology, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand. FAU - Padungros, Panuwat AU - Padungros P AD - Organic Synthesis Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Phayathai Road, Patumwan, Bangkok, 10330, Thailand. FAU - Wongsrisupphakul, Panachai AU - Wongsrisupphakul P AD - Organic Synthesis Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Phayathai Road, Patumwan, Bangkok, 10330, Thailand. FAU - Sa-Ard-Iam, Noppadol AU - Sa-Ard-Iam N AD - Immunology Laboratory, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand. FAU - Mahanonda, Rangsini AU - Mahanonda R AD - Immunology Laboratory, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand. AD - Department of Periodontology, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand. FAU - Matangkasombut, Oranart AU - Matangkasombut O AD - Laboratory of Biotechnology, Chulabhorn Research Institute, Bangkok, 10210, Thailand. AD - Research Unit on Oral Microbiology and Immunology and Department of Microbiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand. FAU - Choo, Min-Kyung AU - Choo MK AUID- ORCID: 0000-0003-1492-7539 AD - Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA. FAU - Ritprajak, Patcharee AU - Ritprajak P AD - Research Unit on Oral Microbiology and Immunology and Department of Microbiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand. Patcharee.R@chula.ac.th. AD - Oral Biology Research Center, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand. Patcharee.R@chula.ac.th. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181120 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Cytokines) RN - 0 (Mannans) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Tlr2 protein, mouse) RN - 0 (Toll-Like Receptor 2) SB - IM MH - Animals MH - Apoptosis/drug effects/immunology MH - Candida/chemistry/cytology/*pathogenicity MH - Candidiasis/metabolism/microbiology/pathology MH - Cell Wall/chemistry MH - Cytokines/metabolism MH - Dendritic Cells/drug effects/*immunology/metabolism MH - Host-Pathogen Interactions MH - Mannans/*toxicity MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Myeloid Differentiation Factor 88/metabolism MH - Th17 Cells/drug effects/*immunology/metabolism MH - Toll-Like Receptor 2/metabolism PMC - PMC6244250 COIS- The authors declare no competing interests. EDAT- 2018/11/22 06:00 MHDA- 2019/12/18 06:00 PMCR- 2018/11/20 CRDT- 2018/11/22 06:00 PHST- 2018/01/17 00:00 [received] PHST- 2018/10/23 00:00 [accepted] PHST- 2018/11/22 06:00 [entrez] PHST- 2018/11/22 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2018/11/20 00:00 [pmc-release] AID - 10.1038/s41598-018-35101-3 [pii] AID - 35101 [pii] AID - 10.1038/s41598-018-35101-3 [doi] PST - epublish SO - Sci Rep. 2018 Nov 20;8(1):17123. doi: 10.1038/s41598-018-35101-3.