Keratinocytes contribute to the recruitment and M1 polarisation of macrophages during  C. albicans colonisation

Xiu-Hao Guan; Yu-Xiao Hong; Rui-Qun Qi; Xing-Hua Gao

doi:10.14715/cmb/2018.64.12.4

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Vol. 64 No. 12: Issue 12

Issue Published : October 2, 2018

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Keratinocytes contribute to the recruitment and M1 polarisation of macrophages during C. albicans colonisation

https://doi.org/10.14715/cmb/2018.64.12.4

Xiu-Hao Guan

Department of Dermatology, The First Hospital of China Medical University, No.155, Nan-Jing Street, Shenyang 110001, Liaoning Province, China

Yu-Xiao Hong

Department of Dermatology, The First Hospital of China Medical University, No.155, Nan-Jing Street, Shenyang 110001, Liaoning Province, China

Rui-Qun Qi

Department of Dermatology, The First Hospital of China Medical University, No.155, Nan-Jing Street, Shenyang 110001, Liaoning Province, China

Xing-Hua Gao

Department of Dermatology, The First Hospital of China Medical University, No.155, Nan-Jing Street, Shenyang 110001, Liaoning Province, China

Corresponding Author(s) : Xing-Hua Gao

qj1167@163.com

Cellular and Molecular Biology, Vol. 64 No. 12: Issue 12
Article Published : September 30, 2018

Abstract

Candida albicans (C. albicans) is an opportunistic human fungal pathogen that colonises the skin. Both keratinocytes and macrophages play crucial roles in host defence against C. albicans. However, the interaction of keratinocytes with macrophages during C. albicans colonisation has not been well studied. In this study, macrophages were cultured in conditioned medium from keratinocytes treated with heat-inactivated C. albicans (CM-C. albicans), macrophage migration and polarised activation and were then assessed by a Transwell assay, flow cytometry, quantitative real-time PCR (qPCR), Western blot and an enzyme-linked immunosorbent assay (ELISA). The results showed that CM-C. albicans-stimulated macrophages display significantly increased migration and phagocytosis, and they display an upregulation of proinflammatory cytokines (tumour necrosis factor alpha (TNF-a), interleukin (IL)-12 and nitric oxide (NO)). Markers characteristic of M1 macrophages, such as human leukocyte antigen (HLA)-DR, CD86 and inducible nitric oxide synthase (iNOS), are upregulated, whereas markers of M2 macrophages, such as mannose receptor (MR) and Arginase 1 (Arg1), are not affected. Additionally, the levels of TNF-a, IL-12 and monocyte chemotactic protein 1 (MCP-1) in CM-C. albicans are markedly upregulated, whereas the levels of IL-4 and IL-10 are not affected. And the CM-C. albicans-induced M1 macrophage polarisation, proinflammatory cytokine production and phagocytosis could be blocked by an anti-TNF-a neutralising antibody. This study showed that keratinocytes may promote macrophage recruitment and M1 polarisation during C. albicans colonisation at least in part by secreting TNF-a.

Keywords

C. albicans Keratinocyte Macrophage M1 polarisation TNF-a.

Guan, X.-H., Hong, Y.-X., Qi, R.-Q., & Gao, X.-H. (2018). Keratinocytes contribute to the recruitment and M1 polarisation of macrophages during C. albicans colonisation. Cellular and Molecular Biology, 64(12), 15–21. https://doi.org/10.14715/cmb/2018.64.12.4

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References

Brown GD, Denning DW, Gow NAR, Levitz SM, Netea MG, White TC. Hidden Killers: Human Fungal Infections. Sci Trans Med 2012; 4: 165.
Samaranayake LP, Fidel PL, Naglik JR, Sweet SP, Teanpaisan R, Coogan MM, et al. Fungal infections associated with HIV infection. Oral Dis 2002; 2: 151–60.
Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C. The Epidemiology and Attributable Outcomes of Candidemia in Adults and Children Hospitalized in the United States: A Propensity Analysis. Clin Infect Dis 2005; 41: 1232–39.
Schiller M, Metze D, Luger TA, Grabbe S, Gunzer M. Immune response modifiers? mode of action. Exp Dermatol 2006; 15: 331–41.
Wollina U, Künkel W, Bulling L, Fünfstück C, Knöll B, Vennewald I, et al. Candida albicans-induced inflammatory response in human keratinocytes. Mycoses 2004; 47: 193–99.
Shiraki Y, Ishibashi Y, Hiruma M, Nishikawa A, Ikeda S. Candida albicans abrogates the expression of interferon-gamma-inducible protein-10 in human keratinocytes. FEMS Immunol Med Microbiol 2008; 54: 122–28.
Bitschar K, Wolz C, Krismer B, Peschel A, Schittek B. Keratinocytes as sensors and central players in the immune defense against Staphylococcus aureus in the skin. J Dermatol Sci 2017; 87: 215–20.
Szolnoky G, Bata-Csörgö Z, Kenderessy AS, Kiss M, Pivarcsi A, Novák Z, et al. A mannose-binding receptor is expressed on human keratinocytes and mediates killing of Candida albicans. J Invest Dermatol 2001; 117: 205–13.
Jones SA. Directing Transition from Innate to Acquired Immunity: Defining a Role for IL-6. J Immunol 2005; 175: 3463–68.
Rossi D, Zlotnik A. The Biology of Chemokines and their Receptors. Annu Rev Immunol 2000; 18: 217–42.
Li M, Chen Q, Shen Y, Liu W. Candida albicansphospholipomannan triggers inflammatory responses of human keratinocytes through Toll-like receptor 2. Exp Dermatol 2009; 18: 603–10.
Romani L. Immunity to fungal infections. Nat Rev Immunol 2011; 11: 275–88.
Xu R, Sun H-F, Williams DW, Jones AV, Al-Hussaini A, Song B, et al. IL-34 Suppresses Candida albicans Induced TNFÎ± Production in M1 Macrophages by Downregulating Expression of Dectin-1 and TLR2. J Immunol Res 2015; 2015: 328146.
Chistiakov DA, Myasoedova VA, Revin VV, Orekhov AN, Bobryshev YV. The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2. Immunobio 2018; 223: 101–11.
Zhou D, Yang K, Chen L, Zhang W, Xu Z, Zuo J, et al. Promising landscape for regulating macrophage polarization: epigenetic viewpoint. Oncotarget 2017; 8: 57693–7706.
Tran VG, Cho HR, Kwon B. IL-33 Priming Enhances Peritoneal Macrophage Activity in Response to Candida albicans. Immune Netw 2014; 14: 201–06.
Ashman RB, Vijayan D, Wells CA. IL-12 and related cytokines: function and regulatory implications in Candida albicans infection. Clin Dev Immunol 2011; 2011: 686597.
Saalbach A, Tremel J, Herbert D, Schwede K, Wandel E, Schirmer C, et al. Anti-Inflammatory Action of Keratinocyte-Derived Vaspin. Am J Pathol 2016; 186: 639–51.
Reales-Calderón JA, Aguilera-Montilla N, Corbí íL, Molero G, Gil C. Proteomic characterization of human proinflammatory M1 and anti-inflammatory M2 macrophages and their response to Candida albicans. PROTEOMICS 2014; 14: 1503–18.
Wu X, Xu W, Feng X, He Y, Liu X, Gao Y, et al. TNF-a mediated inflammatory macrophage polarization contributes to the pathogenesis of steroid-induced osteonecrosis in mice. Int J Immunopathol Pharmacol 2015; 28: 351–61.
Tüzün Y, Antonov M, Dolar N, Wolf R. Keratinocyte cytokine and chemokine receptors. Dermatol Clin 2007; 25: 467–76.
Shiraki Y. Cytokine secretion profiles of human keratinocytes during Trichophyton tonsurans and Arthroderma benhamiae infections. J Med Microbiol 2006; 55: 1175–85.
Jabra-Rizk MA, Kong EF, Tsui C, Nguyen MH, Clancy CJ, Fidel PL, et al. Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework. Infect Immun 2016; 84: 2724–39.
Raponi G, Ghezzi MC, Mancini C, Filadoro F. Culture filtrates and whole heat-killed Candida albicans stimulate human monocytes to release interleukin-6. New Microbiol 1993; 16: 267–74.
Kunze R, Schütz B, Schrödl W, Bernhardt H. Candida albicans clinical isolates inactivated by formalin with different adherence to buccal epithelial cells induce proinflammatory and regulatory cytokines in human peripheral blood mononuclear cells. Mycoses 1999; 42: 529–38.
Tang SX, Moyes DL, Richardson JP, Blagojevic M, Naglik JR. Epithelial discrimination of commensal and pathogenic Candida albicans. Oral Dis 2016; 22: 114–19.
Moyes DL, Runglall M, Murciano C, Shen C, Nayar D, Thavaraj S, et al. A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in epithelial cells. Cell Host Microbe 2010; 8: 225–35.
Hall RA, Noverr MC. Fungal interactions with the human host: exploring the spectrum of symbiosis. Curr Opin Microbiol 2017; 40: 58–64.
da Silva Dantas A, Lee KK, Raziunaite I, Schaefer K, Wagener J, Yadav B, et al. Cell biology of Candida albicans-host interactions. Curr Opin Microbiol 2016; 34: 111–18.
Behfar S, Hassanshahi G, Nazari A, Khorramdelazad H. A brief look at the role of monocyte chemoattractant protein-1 (CCL2) in the pathophysiology of psoriasis. CYTOKINE 2017; 32: 32-35.
Taheri Sarvtin M, Shokohi T, Hajheydari Z, Yazdani J, Hedayati MT. Evaluation of candidal colonization and specific humoral responses against Candida albicans in patients with psoriasis. Int J Dermatol 2014; 53: 555–60.
Javad G, Taheri Sarvtin M, Hedayati MT, Hajheydari Z, Yazdani J, Shokohi T. Evaluation of Candida Colonization and Specific Humoral Responses against Candida albicans in Patients with Atopic Dermatitis. BioMed Res Int 2015; 2015: 849206.
Gil ML, Gozalbo D. About the role of TLR2 and TLR4 in cytokine secretion by murine macrophages in response to Candida albicans. FEMS Immunol Med Microbiol 2006; 46: 1–2.
Jouault T, Ibata-Ombetta S, Takeuchi O, Trinel PA, Sacchetti P, Lefebvre P, et al. Candida albicans phospholipomannan is sensed through toll-like receptors. J Infect Dis 2003; 188: 165–72.
Blasi E, Mucci A, Neglia R, Pezzini F, Colombari B, Radzioch D, et al. Biological importance of the two Toll-like receptors, TLR2 and TLR4, in macrophage response to infection with Candida albicans. FEMS Immunol Med Microbiol 2005; 44: 69–79.
Gantner BN, Simmons RM, Underhill DM. Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J 2005; 24: 1277–86.

References

Brown GD, Denning DW, Gow NAR, Levitz SM, Netea MG, White TC. Hidden Killers: Human Fungal Infections. Sci Trans Med 2012; 4: 165.

Samaranayake LP, Fidel PL, Naglik JR, Sweet SP, Teanpaisan R, Coogan MM, et al. Fungal infections associated with HIV infection. Oral Dis 2002; 2: 151–60.

Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C. The Epidemiology and Attributable Outcomes of Candidemia in Adults and Children Hospitalized in the United States: A Propensity Analysis. Clin Infect Dis 2005; 41: 1232–39.

Schiller M, Metze D, Luger TA, Grabbe S, Gunzer M. Immune response modifiers? mode of action. Exp Dermatol 2006; 15: 331–41.

Wollina U, Künkel W, Bulling L, Fünfstück C, Knöll B, Vennewald I, et al. Candida albicans-induced inflammatory response in human keratinocytes. Mycoses 2004; 47: 193–99.

Shiraki Y, Ishibashi Y, Hiruma M, Nishikawa A, Ikeda S. Candida albicans abrogates the expression of interferon-gamma-inducible protein-10 in human keratinocytes. FEMS Immunol Med Microbiol 2008; 54: 122–28.

Bitschar K, Wolz C, Krismer B, Peschel A, Schittek B. Keratinocytes as sensors and central players in the immune defense against Staphylococcus aureus in the skin. J Dermatol Sci 2017; 87: 215–20.

Szolnoky G, Bata-Csörgö Z, Kenderessy AS, Kiss M, Pivarcsi A, Novák Z, et al. A mannose-binding receptor is expressed on human keratinocytes and mediates killing of Candida albicans. J Invest Dermatol 2001; 117: 205–13.

Jones SA. Directing Transition from Innate to Acquired Immunity: Defining a Role for IL-6. J Immunol 2005; 175: 3463–68.

Rossi D, Zlotnik A. The Biology of Chemokines and their Receptors. Annu Rev Immunol 2000; 18: 217–42.

Li M, Chen Q, Shen Y, Liu W. Candida albicansphospholipomannan triggers inflammatory responses of human keratinocytes through Toll-like receptor 2. Exp Dermatol 2009; 18: 603–10.

Romani L. Immunity to fungal infections. Nat Rev Immunol 2011; 11: 275–88.

Xu R, Sun H-F, Williams DW, Jones AV, Al-Hussaini A, Song B, et al. IL-34 Suppresses Candida albicans Induced TNFÎ± Production in M1 Macrophages by Downregulating Expression of Dectin-1 and TLR2. J Immunol Res 2015; 2015: 328146.

Chistiakov DA, Myasoedova VA, Revin VV, Orekhov AN, Bobryshev YV. The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2. Immunobio 2018; 223: 101–11.

Zhou D, Yang K, Chen L, Zhang W, Xu Z, Zuo J, et al. Promising landscape for regulating macrophage polarization: epigenetic viewpoint. Oncotarget 2017; 8: 57693–7706.

Tran VG, Cho HR, Kwon B. IL-33 Priming Enhances Peritoneal Macrophage Activity in Response to Candida albicans. Immune Netw 2014; 14: 201–06.

Ashman RB, Vijayan D, Wells CA. IL-12 and related cytokines: function and regulatory implications in Candida albicans infection. Clin Dev Immunol 2011; 2011: 686597.

Saalbach A, Tremel J, Herbert D, Schwede K, Wandel E, Schirmer C, et al. Anti-Inflammatory Action of Keratinocyte-Derived Vaspin. Am J Pathol 2016; 186: 639–51.

Reales-Calderón JA, Aguilera-Montilla N, Corbí íL, Molero G, Gil C. Proteomic characterization of human proinflammatory M1 and anti-inflammatory M2 macrophages and their response to Candida albicans. PROTEOMICS 2014; 14: 1503–18.

Wu X, Xu W, Feng X, He Y, Liu X, Gao Y, et al. TNF-a mediated inflammatory macrophage polarization contributes to the pathogenesis of steroid-induced osteonecrosis in mice. Int J Immunopathol Pharmacol 2015; 28: 351–61.

Tüzün Y, Antonov M, Dolar N, Wolf R. Keratinocyte cytokine and chemokine receptors. Dermatol Clin 2007; 25: 467–76.

Shiraki Y. Cytokine secretion profiles of human keratinocytes during Trichophyton tonsurans and Arthroderma benhamiae infections. J Med Microbiol 2006; 55: 1175–85.

Jabra-Rizk MA, Kong EF, Tsui C, Nguyen MH, Clancy CJ, Fidel PL, et al. Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework. Infect Immun 2016; 84: 2724–39.

Raponi G, Ghezzi MC, Mancini C, Filadoro F. Culture filtrates and whole heat-killed Candida albicans stimulate human monocytes to release interleukin-6. New Microbiol 1993; 16: 267–74.

Kunze R, Schütz B, Schrödl W, Bernhardt H. Candida albicans clinical isolates inactivated by formalin with different adherence to buccal epithelial cells induce proinflammatory and regulatory cytokines in human peripheral blood mononuclear cells. Mycoses 1999; 42: 529–38.

Tang SX, Moyes DL, Richardson JP, Blagojevic M, Naglik JR. Epithelial discrimination of commensal and pathogenic Candida albicans. Oral Dis 2016; 22: 114–19.

Moyes DL, Runglall M, Murciano C, Shen C, Nayar D, Thavaraj S, et al. A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in epithelial cells. Cell Host Microbe 2010; 8: 225–35.

Hall RA, Noverr MC. Fungal interactions with the human host: exploring the spectrum of symbiosis. Curr Opin Microbiol 2017; 40: 58–64.

da Silva Dantas A, Lee KK, Raziunaite I, Schaefer K, Wagener J, Yadav B, et al. Cell biology of Candida albicans-host interactions. Curr Opin Microbiol 2016; 34: 111–18.

Behfar S, Hassanshahi G, Nazari A, Khorramdelazad H. A brief look at the role of monocyte chemoattractant protein-1 (CCL2) in the pathophysiology of psoriasis. CYTOKINE 2017; 32: 32-35.

Taheri Sarvtin M, Shokohi T, Hajheydari Z, Yazdani J, Hedayati MT. Evaluation of candidal colonization and specific humoral responses against Candida albicans in patients with psoriasis. Int J Dermatol 2014; 53: 555–60.

Javad G, Taheri Sarvtin M, Hedayati MT, Hajheydari Z, Yazdani J, Shokohi T. Evaluation of Candida Colonization and Specific Humoral Responses against Candida albicans in Patients with Atopic Dermatitis. BioMed Res Int 2015; 2015: 849206.

Gil ML, Gozalbo D. About the role of TLR2 and TLR4 in cytokine secretion by murine macrophages in response to Candida albicans. FEMS Immunol Med Microbiol 2006; 46: 1–2.

Jouault T, Ibata-Ombetta S, Takeuchi O, Trinel PA, Sacchetti P, Lefebvre P, et al. Candida albicans phospholipomannan is sensed through toll-like receptors. J Infect Dis 2003; 188: 165–72.

Blasi E, Mucci A, Neglia R, Pezzini F, Colombari B, Radzioch D, et al. Biological importance of the two Toll-like receptors, TLR2 and TLR4, in macrophage response to infection with Candida albicans. FEMS Immunol Med Microbiol 2005; 44: 69–79.

Gantner BN, Simmons RM, Underhill DM. Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J 2005; 24: 1277–86.

Author biographies is not available.