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Candida albicans Elicits Pro-Inflammatory Differential Gene Expression in Intestinal Peyer’s Patches

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Abstract

The details of how gut-associated lymphoid tissues such as Peyer’s patches (PPs) in the small intestine play a role in immune surveillance, microbial differentiation and the mucosal barrier protection in response to fungal organisms such as Candida albicans are still unclear. We particularly focus on PPs as they are the immune sensors and inductive sites of the gut that influence inflammation and tolerance. We have previously demonstrated that CD11c+ phagocytes that include dendritic cells and macrophages are located in the sub-epithelial dome within PPs sample C. albicans. To gain insight on how specific cells within PPs sense and respond to the sampling of fungi, we gavaged naïve mice with C. albicans strains ATCC 18804 and SC5314 as well as Saccharomyces cerevisiae. We measured the differential gene expression of sorted CD45+ B220+ B-cells, CD3+ T-cells and CD11c+ DCs within the first 24 h post-gavage using nanostring nCounter® technology. The results reveal that at 24 h, PP phagocytes were the cell type that displayed differential gene expression. These phagocytes were able to sample C. albicans and discriminate between strains. In particular, strain ATCC 18804 upregulated fungal-specific pro-inflammatory genes pertaining to innate and adaptive immune responses. Interestingly, PP CD11c+ phagocytes also differentially expressed genes in response to C. albicans that were important in the protection of the mucosal barrier. These results highlight that the mucosal barrier not only responds to C. albicans, but also aids in the protection of the host.

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References

  1. Kumamoto CA. Inflammation and gastrointestinal Candida colonization. Curr Opin Microbiol. 2011;14(4):386–91. https://doi.org/10.1016/j.mib.2011.07.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Tong Y, Tang J. Candida albicans infection and intestinal immunity. Microbiol Res. 2017;198:27–35. https://doi.org/10.1016/j.micres.2017.02.002.

    Article  CAS  PubMed  Google Scholar 

  3. Bohringer M, Pohlers S, Schulze S, Albrecht-Eckardt D, Piegsa J, Weber M, et al. Candida albicans infection leads to barrier breakdown and a MAPK/NF-kappaB mediated stress response in the intestinal epithelial cell line C2BBe1. Cell Microbiol. 2016;18(7):889–904. https://doi.org/10.1111/cmi.12566.

    Article  CAS  PubMed  Google Scholar 

  4. Liguori G, Lamas B, Richard ML, Brandi G, da Costa G, Hoffmann TW, et al. Fungal dysbiosis in Mucosa-associated microbiota of crohn’s disease patients. J Crohns Colitis. 2016;10(3):296–305. https://doi.org/10.1093/ecco-jcc/jjv209.

    Article  PubMed  Google Scholar 

  5. Frykman PK, Nordenskjold A, Kawaguchi A, Hui TT, Granstrom AL, Cheng Z, et al. Characterization of bacterial and fungal microbiome in children with Hirschsprung disease with and without a history of enterocolitis: a multicenter study. PLoS ONE. 2015;10(4):e0124172. https://doi.org/10.1371/journal.pone.0124172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jawhara S, Thuru X, Standaert-Vitse A, Jouault T, Mordon S, Sendid B, et al. Colonization of mice by Candida albicans is promoted by chemically induced colitis and augments inflammatory responses through galectin-3. J Infect Dis. 2008;197(7):972–80. https://doi.org/10.1086/528990.

    Article  CAS  PubMed  Google Scholar 

  7. Iliev ID, Funari VA, Taylor KD, Nguyen Q, Reyes CN, Strom SP, et al. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science. 2012;336(6086):1314–7. https://doi.org/10.1126/science.1221789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Koh AY. Identifying host immune effectors critical for protection against Candida albicans infections. Virulence. 2016;7(7):745–7. https://doi.org/10.1080/21505594.2016.1205177.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Koh AY. Murine models of Candida gastrointestinal colonization and dissemination. Eukaryot Cell. 2013;12(11):1416–22. https://doi.org/10.1128/EC.00196-13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ahlawat S, De Jesus M, Khare K, Cole RA, Mantis NJ. Three-dimensional reconstruction of murine Peyer’s patches from immunostained cryosections. Microsc Microanal. 2014;20(1):198–205. https://doi.org/10.1017/S1431927613013640.

    Article  CAS  PubMed  Google Scholar 

  11. Singh N, Gallagher HC, Song R, Dhinsa JK, Ostroff GR, De Jesus M. RNA isolation from Peyer’s patch lymphocytes and mononuclear phagocytes to determine gene expression profiles using nanostring technology. J Biol Methods. 2018;5(3):e95. https://doi.org/10.14440/jbm.2018.246.

    Article  PubMed  PubMed Central  Google Scholar 

  12. De Jesus M, Ostroff GR, Levitz SM, Bartling TR, Mantis NJ. A population of Langerin-positive dendritic cells in murine Peyer’s patches involved in sampling beta-glucan microparticles. PLoS ONE. 2014;9(3):e91002. https://doi.org/10.1371/journal.pone.0091002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Goyer M, Loiselet A, Bon F, L’Ollivier C, Laue M, Holland G, et al. Intestinal cell tight junctions limit invasion of Candida albicans through active penetration and endocytosis in the early stages of the interaction of the fungus with the intestinal barrier. PLoS ONE. 2016;11(3):e0149159. https://doi.org/10.1371/journal.pone.0149159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Rast TJ, Kullas AL, Southern PJ, Davis DA. Human epithelial cells discriminate between commensal and pathogenic interactions with Candida albicans. PLoS ONE. 2016;11(4):e0153165. https://doi.org/10.1371/journal.pone.0153165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. De Jesus M, Rodriguez AE, Yagita H, Ostroff GR, Mantis NJ. Sampling of Candida albicans and Candida tropicalis by Langerin-positive dendritic cells in mouse Peyer’s patches. Immunol Lett. 2015;168(1):64–72. https://doi.org/10.1016/j.imlet.2015.09.008.

    Article  CAS  PubMed  Google Scholar 

  16. Albac S, Schmitz A, Lopez-Alayon C, d’Enfert C, Sautour M, Ducreux A, et al. Candida albicans is able to use M cells as a portal of entry across the intestinal barrier in vitro. Cell Microbiol. 2016;18(2):195–210. https://doi.org/10.1111/cmi.12495.

    Article  CAS  PubMed  Google Scholar 

  17. Bonnardel J, Da Silva C, Masse M, Montanana-Sanchis F, Gorvel JP, Lelouard H. Gene expression profiling of the Peyer’s patch mononuclear phagocyte system. Genom Data. 2015;5:21–4. https://doi.org/10.1016/j.gdata.2015.05.002.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Maroilley T, Berri M, Lemonnier G, Esquerre D, Chevaleyre C, Melo S, et al. Immunome differences between porcine ileal and jejunal Peyer’s patches revealed by global transcriptome sequencing of gut-associated lymphoid tissues. Sci Rep. 2018;8(1):9077. https://doi.org/10.1038/s41598-018-27019-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Da Silva C, Wagner C, Bonnardel J, Gorvel JP, Lelouard H. The Peyer’s patch mononuclear phagocyte system at steady state and during infection. Front Immunol. 2017;8:1254. https://doi.org/10.3389/fimmu.2017.01254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bonifazi P, Zelante T, D’Angelo C, De Luca A, Moretti S, Bozza S, et al. Balancing inflammation and tolerance in vivo through dendritic cells by the commensal Candida albicans. Mucosal Immunol. 2009;2(4):362–74. https://doi.org/10.1038/mi.2009.17.

    Article  CAS  PubMed  Google Scholar 

  21. Xu W, Solis NV, Filler SG, Mitchell AP. Pathogen gene expression profiling during infection using a nanostring ncounter platform. Methods Mol Biol. 2016;1361:57–65. https://doi.org/10.1007/978-1-4939-3079-1_3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Marakalala MJ, Vautier S, Potrykus J, Walker LA, Shepardson KM, Hopke A, et al. Differential adaptation of Candida albicans in vivo modulates immune recognition by dectin-1. PLoS Pathog. 2013;9(4):e1003315. https://doi.org/10.1371/journal.ppat.1003315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. https://doi.org/10.1186/s13059-014-0550-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen J, Tambalo M, Barembaum M, Ranganathan R, Simoes-Costa M, Bronner ME, et al. A systems-level approach reveals new gene regulatory modules in the developing ear. Development. 2017;144(8):1531–43. https://doi.org/10.1242/dev.148494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ngo VL, Abo H, Maxim E, Harusato A, Geem D, Medina-Contreras O, et al. A cytokine network involving IL-36gamma, IL-23, and IL-22 promotes antimicrobial defense and recovery from intestinal barrier damage. Proc Natl Acad Sci USA. 2018;115(22):E5076–85. https://doi.org/10.1073/pnas.1718902115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gaffen SL, Jain R, Garg AV, Cua DJ. The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing. Nat Rev Immunol. 2014;14(9):585–600. https://doi.org/10.1038/nri3707.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zelante T, De Luca A, Bonifazi P, Montagnoli C, Bozza S, Moretti S, et al. IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur J Immunol. 2007;37(10):2695–706. https://doi.org/10.1002/eji.200737409.

    Article  CAS  PubMed  Google Scholar 

  28. Wuyts W, Van Wesenbeeck L, Morales-Piga A, Ralston S, Hocking L, Vanhoenacker F, et al. Evaluation of the role of RANK and OPG genes in Paget’s disease of bone. Bone. 2001;28(1):104–7. https://doi.org/10.1016/S8756-3282(00)00411-7.

    Article  CAS  PubMed  Google Scholar 

  29. Nakamura Y, Kimura S, Hase K. M cell-dependent antigen uptake on follicle-associated epithelium for mucosal immune surveillance. Inflamm Regen. 2018;38:15. https://doi.org/10.1186/s41232-018-0072-y72.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Kanaya T, Ohno H. The mechanisms of M-cell differentiation. Biosci Microbiota Food Health. 2014;33(3):91–7. https://doi.org/10.12938/bmfh.33.912013-024.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Knoop KA, Kumar N, Butler BR, Sakthivel SK, Taylor RT, Nochi T, et al. RANKL is necessary and sufficient to initiate development of antigen-sampling M cells in the intestinal epithelium. J Immunol. 2009;183(9):5738–47. https://doi.org/10.4049/jimmunol.0901563jimmunol.0901563.

    Article  CAS  PubMed  Google Scholar 

  32. Okada S, Markle JG, Deenick EK, Mele F, Averbuch D, Lagos M, et al. Immunodeficiencies. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Science. 2015;349(6248):606–13. https://doi.org/10.1126/science.aaa4282.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Robinson RT, Huppler AR. The Goldilocks model of immune symbiosis with Mycobacteria and Candida colonizers. Cytokine. 2017;97:49–65. https://doi.org/10.1016/j.cyto.2017.05.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. De Luca A, Montagnoli C, Zelante T, Bonifazi P, Bozza S, Moretti S, et al. Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc. J Immunol. 2007;179(9):5999–6008.

    Article  PubMed  Google Scholar 

  35. Altmeier S, Toska A, Sparber F, Teijeira A, Halin C, LeibundGut-Landmann S. IL-1 coordinates the neutrophil response to C. albicans in the oral mucosa. PLoS Pathog. 2016;12(9):1005882. https://doi.org/10.1371/journal.ppat.1005882.

    Article  CAS  Google Scholar 

  36. Cambi A, Gijzen K, de Vries IJ, Torensma R, Joosten B, Adema GJ, et al. An antigen-uptake receptor for Candida albicans on dendritic cells. Eur J Immunol. 2003;33(2):532–8. https://doi.org/10.1002/immu.200310029.

    Article  CAS  PubMed  Google Scholar 

  37. Cambi A, Netea MG, Mora-Montes HM, Gow NA, Hato SV, Lowman DW, et al. Dendritic cell interaction with Candida albicans critically depends on N-linked mannan. J Biol Chem. 2008;283(29):20590–9. https://doi.org/10.1074/jbc.M709334200M709334200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Takahara K, Yashima Y, Omatsu Y, Yoshida H, Kimura Y, Kang YS, et al. Functional comparison of the mouse DC-SIGN, SIGNR1, SIGNR3 and Langerin, C-type lectins. Int Immunol. 2004;16(6):819–29. https://doi.org/10.1093/intimm/dxh084dxh084.

    Article  CAS  PubMed  Google Scholar 

  39. Gao N, Yu FS. Chitinase 3-Like 1 promotes Candida albicans killing and preserves corneal structure and function by controlling host antifungal responses. Infect Immun. 2015;83(10):4154–64. https://doi.org/10.1128/IAI.00980-15IAI.00980-15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Low D, Subramaniam R, Lin L, Aomatsu T, Mizoguchi A, Ng A, et al. Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9. Oncotarget. 2015;6(34):36535–50. https://doi.org/10.18632/oncotarget.54405440.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Forssmann U, Uguccioni M, Loetscher P, Dahinden CA, Langen H, Thelen M, et al. Eotaxin-2, a novel CC chemokine that is selective for the chemokine receptor CCR41, and acts like eotaxin on human eosinophil and basophil leukocytes. J Exp Med. 1997;185(12):2171–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Williams EJ, Haque S, Banks C, Johnson P, Sarsfield P, Sheron N. Distribution of the interleukin-8 receptors, CXCR42 and CXCR42, in inflamed gut tissue. J Pathol. 2000;192(4):533–9.

    Article  CAS  PubMed  Google Scholar 

  43. Santoni G, Gismondi A, Liu JH, Punturieri A, Santoni A, Frati L, et al. Candida albicans expresses a fibronectin receptor antigenically related to alpha 5 beta 1 integrin. Microbiology. 1994;140(Pt11):2971–9. https://doi.org/10.1099/13500872-140-11-2971.

    Article  CAS  PubMed  Google Scholar 

  44. Tronchin G, Bouchara JP, Robert R, Senet JM. Adherence of Candida albicans germ tubes to plastic: ultrastructural and molecular studies of fibrillar adhesins. Infect Immun. 1988;56(8):1987–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Alteber Z, Sharbi-Yunger A, Pevsner-Fischer M, Blat D, Roitman L, Tzehoval E, et al. The anti-inflammatory IFITM genes ameliorate colitis and partially protect from tumorigenesis by changing immunity and microbiota. Immunol Cell Biol. 2018;96(3):284–97. https://doi.org/10.1111/imcb.12000.

    Article  CAS  PubMed  Google Scholar 

  46. Gulati K, Gangele K, Agarwal N, Jamsandekar M, Kumar D, Poluri KM. Molecular cloning and biophysical characterization of CXCL3 chemokine. Int J Biol Macromol. 2018;107(Pt A):575–84. https://doi.org/10.1016/j.ijbiomac.2017.09.032.

    Article  CAS  PubMed  Google Scholar 

  47. Dwivedi P, Greis KD. Granulocyte colony-stimulating factor receptor signaling in severe congenital neutropenia, chronic neutrophilic leukemia, and related malignancies. Exp Hematol. 2017;46:9–20. https://doi.org/10.1016/j.exphem.2016.10.008.

    Article  CAS  PubMed  Google Scholar 

  48. Mehta HM, Malandra M, Corey SJ. G-CSF and GM-CSF in Neutropenia. J Immunol. 2015;195(4):1341–9. https://doi.org/10.4049/jimmunol.1500861195/4/1341.

    Article  CAS  PubMed  Google Scholar 

  49. Netea MG, Simon A, van de Veerdonk F, Kullberg BJ, Van der Meer JW, Joosten LA. IL-1beta processing in host defense: beyond the inflammasomes. PLoS Pathog. 2010;6(2):e1000661. https://doi.org/10.1371/journal.ppat.1000661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Vonk AG, Netea MG, van Krieken JH, Iwakura Y, van der Meer JWM, Kullberg BJ. Endogenous interleukin (IL)–1α and IL-1β are crucial for host defense against disseminated Candidiasis. J Infect Dis. 2006;193(10):1419–26. https://doi.org/10.1086/503363.

    Article  CAS  PubMed  Google Scholar 

  51. Salvi V, Vermi W, Gianello V, Lonardi S, Gagliostro V, Naldini A, et al. Dendritic cell-derived VEGF-A plays a role in inflammatory angiogenesis of human secondary lymphoid organs and is driven by the coordinated activation of multiple transcription factors. Oncotarget. 2016;7(26):39256–69. https://doi.org/10.18632/oncotarget.96849684.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Laurent S, Carrega P, Saverino D, Piccioli P, Camoriano M, Morabito A, et al. CTLA-4 is expressed by human monocyte-derived dendritic cells and regulates their functions. Hum Immunol. 2010;71(10):934–41. https://doi.org/10.1016/j.humimm.2010.07.007.

    Article  CAS  PubMed  Google Scholar 

  53. Guimbaud R, Abitbol V, Bertrand V, Quartier G, Chauvelot-Moachon L, Giroud J, et al. Leukemia inhibitory factor involvement in human ulcerative colitis and its potential role in malignant course. Eur Cytokine Netw. 1998;9(4):607–12.

    CAS  PubMed  Google Scholar 

  54. Smeekens SP, van de Veerdonk FL, Joosten LA, Jacobs L, Jansen T, Williams DL, et al. The classical CD14(+)(+) CD16(-) monocytes, but not the patrolling CD14(+) CD16(+) monocytes, promote Th17 responses to Candida albicans. Eur J Immunol. 2011;41(10):2915–24. https://doi.org/10.1002/eji.201141418.

    Article  CAS  PubMed  Google Scholar 

  55. Tada H, Nemoto E, Shimauchi H, Watanabe T, Mikami T, Matsumoto T, et al. Saccharomyces cerevisiae- and Candida albicans-derived mannan induced production of tumor necrosis factor alpha by human monocytes in a CD14- and Toll-like receptor 4-dependent manner. Microbiol Immunol. 2002;46(7):503–12.

    Article  CAS  PubMed  Google Scholar 

  56. Meri T, Blom AM, Hartmann A, Lenk D, Meri S, Zipfel PF. The hyphal and yeast forms of Candida albicans bind the complement regulator C4b-binding protein. Infect Immun. 2004;72(11):6633–41. https://doi.org/10.1128/IAI.72.11.6633-6641.2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Rambach G, Speth C. Complement in Candida albicans infections. Front Biosci (Elite Ed). 2009;1:1–12.

    PubMed  Google Scholar 

  58. Fordham JB, Hua J, Morwood SR, Schewitz-Bowers LP, Copland DA, Dick AD, et al. Environmental conditioning in the control of macrophage thrombospondin-1 production. Sci Rep. 2012;2:512. https://doi.org/10.1038/srep00512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Martin-Manso G, Navarathna DH, Galli S, Soto-Pantoja DR, Kuznetsova SA, Tsokos M, et al. Endogenous thrombospondin-1 regulates leukocyte recruitment and activation and accelerates death from systemic candidiasis. PLoS ONE. 2012;7(11):e48775. https://doi.org/10.1371/journal.pone.0048775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Yi YS. Functional role of milk fat globule-epidermal growth factor VIII in macrophage-mediated inflammatory responses and inflammatory/autoimmune diseases. Mediators Inflamm. 2016;2016:5628486. https://doi.org/10.1155/2016/5628486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Chogle A, Bu HF, Wang X, Brown JB, Chou PM, Tan XD. Milk fat globule-EGF factor 8 is a critical protein for healing of dextran sodium sulfate-induced acute colitis in mice. Mol Med. 2011;17(5–6):502–7. https://doi.org/10.2119/molmed.2010.00074.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Gaffen SL, Hernandez-Santos N, Peterson AC. IL-17 signaling in host defense against Candida albicans. Immunol Res. 2011;50(2–3):181–7. https://doi.org/10.1007/s12026-011-8226-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Conti HR, Gaffen SL. IL-17-mediated immunity to the opportunistic fungal pathogen Candida albicans. J Immunol. 2015;195(3):780–8. https://doi.org/10.4049/jimmunol.1500909.

    Article  CAS  PubMed  Google Scholar 

  64. Chin VK, Foong KJ, Maha A, Rusliza B, Norhafizah M, Chong PP. Early expression of local cytokines during systemic Candida albicans infection in a murine intravenous challenge model. Biomed Rep. 2014;2(6):869–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Arango Duque G, Descoteaux A. Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol. 2014;5:491. https://doi.org/10.3389/fimmu.2014.00491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. van Enckevort FH, Netea MG, Hermus AR, Sweep CG, Meis JF, Van der Meer JW, et al. Increased susceptibility to systemic candidiasis in interleukin-6 deficient mice. Med Mycol. 1999;37(6):419–26.

    Article  PubMed  Google Scholar 

  67. Triebel T, Grillhosl B, Kacani L, Lell CP, Fuchs A, Speth C, et al. Importance of the terminal complement components for immune defence against Candida. Int J Med Microbiol. 2003;292(7–8):527–36. https://doi.org/10.1078/1438-4221-00211.

    Article  CAS  PubMed  Google Scholar 

  68. Wang S, Song R, Wang Z, Jing Z, Ma J. S100A8/A9 in inflammation. Front Immunol. 2018;9:1298. https://doi.org/10.3389/fimmu.2018.01298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Yano J, Kolls JK, Happel KI, Wormley F, Wozniak KL, Fidel PL Jr. The acute neutrophil response mediated by S100 alarmins during vaginal Candida infections is independent of the Th17-pathway. PLoS ONE. 2012;7(9):e46311. https://doi.org/10.1371/journal.pone.0046311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Yano J, Lilly E, Barousse M, Fidel PL Jr. Epithelial cell-derived S100 calcium-binding proteins as key mediators in the hallmark acute neutrophil response during Candida vaginitis. Infect Immun. 2010;78(12):5126–37. https://doi.org/10.1128/IAI.00388-10IAI.00388-10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Yano J, Noverr MC, Fidel PL Jr. Cytokines in the host response to Candida vaginitis: identifying a role for non-classical immune mediators, S100 alarmins. Cytokine. 2012;58(1):118–28. https://doi.org/10.1016/j.cyto.2011.11.021S1043-4666(11)00831-3.

    Article  CAS  PubMed  Google Scholar 

  72. Bjerknes R, Aarskog D. Priming of human polymorphonuclear neutrophilic leukocytes by insulin-like growth factor I: increased phagocytic capacity, complement receptor expression, degranulation, and oxidative burst. J Clin Endocrinol Metab. 1995;80(6):1948–55. https://doi.org/10.1210/jcem.80.6.7775645.

    Article  CAS  PubMed  Google Scholar 

  73. Halim TY, MacLaren A, Romanish MT, Gold MJ, McNagny KM, Takei F. Retinoic-acid-receptor-related orphan nuclear receptor alpha is required for natural helper cell development and allergic inflammation. Immunity. 2012;37(3):463–74. https://doi.org/10.1016/j.immuni.2012.06.012.

    Article  CAS  PubMed  Google Scholar 

  74. Vulcano M, Albanesi C, Stoppacciaro A, Bagnati R, D’Amico G, Struyf S, et al. Dendritic cells as a major source of macrophage-derived chemokine/CCL22 in vitro and in vivo. Eur J Immunol. 2001;31(3):812–22. https://doi.org/10.1002/1521-4141(200103)31:3%3c812:AID-IMMU812%3e3.0.CO;2-L.

    Article  CAS  PubMed  Google Scholar 

  75. Yun B, Lee H, Jayaraja S, Suram S, Murphy RC, Leslie CC. Prostaglandins from cytosolic phospholipase A2alpha/cyclooxygenase-1 pathway and mitogen-activated protein kinases regulate gene expression in Candida albicans-infected macrophages. J Biol Chem. 2016;291(13):7070–86. https://doi.org/10.1074/jbc.M116.714873M116.714873.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Yuan X, Hua X, Wilhelmus KR. Proinflammatory chemokines during Candida albicans keratitis. Exp Eye Res. 2010;90(3):413–9. https://doi.org/10.1016/j.exer.2009.12.001.

    Article  CAS  PubMed  Google Scholar 

  77. Vautier S, Drummond RA, Redelinghuys P, Murray GI, MacCallum DM, Brown GD. Dectin-1 is not required for controlling Candida albicans colonization of the gastrointestinal tract. Infect Immun. 2012;80(12):4216–22. https://doi.org/10.1128/IAI.00559-12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Morgan E, Varro R, Sepulveda H, Ember JA, Apgar J, Wilson J, et al. Cytometric bead array: a multiplexed assay platform with applications in various areas of biology. Clin Immunol. 2004;110(3):252–66. https://doi.org/10.1016/j.clim.2003.11.017.

    Article  CAS  PubMed  Google Scholar 

  79. Castillo L, MacCallum DM. Cytokine measurement using cytometric bead arrays. Methods Mol Biol. 2012;845:425–34. https://doi.org/10.1007/978-1-61779-539-8_29.

    Article  CAS  PubMed  Google Scholar 

  80. Zuo T, Ng SC. The gut microbiota in the pathogenesis and therapeutics of inflammatory bowel disease. Front Microbiol. 2018;9:2247. https://doi.org/10.3389/fmicb.2018.02247.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Xiao L, Feng Q, Liang S, Sonne SB, Xia Z, Qiu X, et al. A catalog of the mouse gut metagenome. Nat Biotechnol. 2015;33(10):1103–8. https://doi.org/10.1038/nbt.3353.

    Article  CAS  PubMed  Google Scholar 

  82. Underhill DM, Iliev ID. The mycobiota: interactions between commensal fungi and the host immune system. Nat Rev Immunol. 2014;14(6):405–16. https://doi.org/10.1038/nri3684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Soll DR, Galask R, Schmid J, Hanna C, Mac K, Morrow B. Genetic dissimilarity of commensal strains of Candida spp. carried in different anatomical locations of the same healthy women. J Clin Microbiol. 1991;29(8):1702–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Huffnagle GB, Noverr MC. The emerging world of the fungal microbiome. Trends Microbiol. 2013;21(7):334–41. https://doi.org/10.1016/j.tim.2013.04.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Brun P, Castagliuolo I, Di Leo V, Buda A, Pinzani M, Palu G, et al. Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2007;292(2):G518–25. https://doi.org/10.1152/ajpgi.00024.2006.

    Article  CAS  PubMed  Google Scholar 

  86. Bonifazi P, Zelante T, D’Angelo C, De Luca A, Moretti S, Bozza S, et al. Balancing inflammation and tolerance in vivo through dendritic cells by the commensal Candida albicans. Mucosal Immunol. 2009;2(4):362–74. https://doi.org/10.1038/mi.2009.17mi200917.

    Article  CAS  PubMed  Google Scholar 

  87. Drakes ML, Lu L, Mckenna HJ, Thomson AW. The influence of collagen, fibronectin, and laminin on the maturation of dendritic cell progenitors propagated from normal or Flt3-ligand-treated mouse liver. Boston: Springer; 1997.

    Book  Google Scholar 

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Acknowledgements

We thank the Wadsworth Center Applied Genomic Technologies Core and the Wadsworth Center Biochemistry and Immunology Core. We thank Dr. Kelly Miller of Nanostring Technologies for assistance with technical support and data analysis. We thank Yannick David for his help in generating the PP model. We thank Dr. Sudha Chaturvedi at the Wadsworth Center Mycology laboratory for providing C. albicans strain ATCC 18804. We thank Dr. Aaron Mitchell at Carnegie Mellon University for providing C. albicans strain SC5314. We thank Dr. Kimberly McClive-Reed of Health Research, Inc. for critical reading of this manuscript. M.D.J. was supported by the University at Albany and Wadsworth Center start-up funds. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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Singh, N., Kim, H.C., Song, R. et al. Candida albicans Elicits Pro-Inflammatory Differential Gene Expression in Intestinal Peyer’s Patches. Mycopathologia 184, 461–478 (2019). https://doi.org/10.1007/s11046-019-00349-4

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