Heat-killed Candida albicans augments synthetic bacterial component-induced proinflammatory cytokine production
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Candida albicans can enhance the invasion of oral epithelial cells by Porphyromonas gingivalis, although the fungus is not a periodontal pathogen. In this study, we investigated whether C. albicans augments proinflammatory cytokine production by mouse macrophage-like J774.1 cells incubated with synthetic bacterial components. Mouse macrophage-like J774.1 cells, mouse primary splenocytes, human THP-1 cells, and A549 cells were pretreated with or without heat-killed C. albicans (HKCA) or substitutes for C. albicans cell wall components in 96-well flat-bottomed plates. Cells were then washed and incubated with Pam3CSK4, a Toll-like receptor (TLR) 2 ligand, or lipid A, a TLR4 ligand. Culture supernatants were analyzed by ELISA for secreted IL-6, MCP-1, TNF-α, and IL-8. HKCA augmented TLR ligand-induced proinflammatory cytokine production by J774.1 cells, mouse splenocytes, and THP-1 cells, but not A549 cells. However, IL-6, MCP-1, and TNF-α production induced by Pam3CSK4 or lipid A was not augmented when cells were pretreated with curdlan, a dectin-1 ligand, or mannan, a dectin-2 ligand. In contrast, pretreatment of cells with TLR ligands upregulated the production of IL-6 and TNF-α, but not MCP-1, induced by Pam3CSK4 or lipid A. The results suggest that C. albicans augments synthetic bacterial component-induced cytokine production by J774.1 cells via the TLR pathway, but not the dectin-1 or dectin-2 pathway.
This study was supported by a Grant-in-Aid for Scientific Research from the Ohu University School of Dentistry.
Compliance with ethical standards
All animals were handled and cared for according to guidelines for the proper conduct of animal experiments (Japan) published by the Science Council of Japan. All procedures were approved by the Institutional Animal Care and Use Committee of Ohu University.
Conflict of interest
The authors declare that they have no conflict of interest.
- Biondo C, Malara A, Costa A, Signorino G, Cardile F, Midiri A, Galbo R, Papasergi S, Domina M, Pugliese M, Teti G, Mancuso G, Beninati C (2012) Recognition of fungal RNA by TLR7 has a nonredundant role in host defense against experimental candidiasis. Eur J Immunol 42:2632–2643CrossRefGoogle Scholar
- Jouault T, El Abed-El Behi M, Martinez-Esparza M, Breuilh L, Trinel PA, Chamaillard M, Trottein F, Poulain D (2006) Specific recognition of Candida albicans by macrophages requires galectin-3 to discriminate Saccharomyces cerevisiae and needs association with TLR2 for signaling. J Immunol 177:4679–4687CrossRefGoogle Scholar
- Kushida T, Makino T, Tomomura M, Tomomura A, Sakagami H (2011) Enhancement of Dectin-2 gene expression by lignin-carbohydrate complex from Lentinus edodes mycelia extract (LEM) in a mouse macrophage-like cell line. Anticancer Res 31:1241–1248Google Scholar
- Masuda T, Deng X, Tamai R (2009) Mouse macrophages primed with alendronate down-regulate monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) production in response to Toll-like receptor (TLR) 2 and TLR4 agonist via Smad3 activation. Int Immunopharmacol 9:1115–1121CrossRefGoogle Scholar
- Miyazato A, Nakamura K, Yamamoto N, Mora-Montes HM, Tanaka M, Abe Y, Tanno D, Inden K, Gang X, Ishii K, Takeda K, Akira S, Saijo S, Iwakura Y, Adachi Y, Ohno N, Mitsutake K, Gow NA, Kaku M, Kawakami K (2009) Toll-like receptor 9-dependent activation of myeloid dendritic cells by deoxynucleic acids from Candida albicans. Infect Immun 77:3056–3064CrossRefGoogle Scholar
- Nomura F, Akashi S, Sakao Y, Sato S, Kawai T, Matsumoto M, Nakanishi K, Kimoto M, Miyake K, Takeda K, Akira S (2000) Cutting edge: endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface toll-like receptor 4 expression. J Immunol 164:3476–3479CrossRefGoogle Scholar
- Plantinga TS, Johnson MD, Scott WK, van de Vosse E, Velez Edwards DR, Smith PB, Alexander BD, Yang JC, Kremer D, Laird GM, Oosting M, Joosten LA, van der Meer JW, van Dissel JT, Walsh TJ, Perfect JR, Kullberg BJ, Netea MG (2012) Toll-like receptor 1 polymorphisms increase susceptibility to candidemia. J Infect Dis 205:934–943CrossRefGoogle Scholar
- Quintin J, Saeed S, Martens JHA, Giamarellos-Bourboulis EJ, Ifrim DC, Logie C, Jacobs L, Jansen T, Kullberg BJ, Wijmenga C, Joosten LAB, Xavier RJ, van der Meer JWM, Stunnenberg HG, Netea MG (2012) Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe 12:223–232CrossRefGoogle Scholar
- Saijo S, Ikeda S, Yamabe K, Kakuta S, Ishigame H, Akitsu A, Fujikado N, Kusaka T, Kubo S, Chung SH, Komatsu R, Miura N, Adachi Y, Ohno N, Shibuya K, Yamamoto N, Kawakami K, Yamasaki S, Saito T, Akira S, Iwakura Y (2010) Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. Immunity 32:681–691CrossRefGoogle Scholar
- Tanne A, Ma B, Boudou F, Tailleux L, Botella H, Badell E, Levillain F, Taylor ME, Drickamer K, Nigou J, Dobos KM, Puzo G, Vestweber D, Wild MK, Marcinko M, Sobieszczuk P, Stewart L, Lebus D, Gicquel B, Neyrolles O (2009) A murine DC-SIGN homologue contributes to early host defense against Mycobacterium tuberculosis. J Exp Med 206:2205–2220CrossRefGoogle Scholar
- Wu SY, Huang JH, Chen WY, Chan YC, Lin CH, Chen YC, Liu FT, Wu-Hsieh BA (2017) Cell intrinsic galectin-3 attenuates neutrophil ROS-dependent killing of Candida by modulating CR3 downstream Syk activation. Front Immunol 8:48Google Scholar
- Xie Y, Xu M, Xiao Y, Liu Z, Jiang C, Kuang X, Wang C, Wu H, Peng J, Li C, Wang Y, Liu H, Liu B, Zhang X, Zhao F, Zeng T, Liu S, Wu Y (2017) Treponema pallidum flagellin FlaA2 induces IL-6 secretion in THP-1 cells via the Toll-like receptor 2 signaling pathway. Mol Immunol 81:42–51CrossRefGoogle Scholar