1887

Abstract

Although characterization of the baseline oral microbiota has been discussed, the current literature seems insufficient to draw a definitive conclusion on the interactions between the microbes themselves or with the host. This study focuses on the spatial and temporal characteristics of the oral microbial ecosystem in a mouse model and its crosstalk with host immune cells in homeostasis. The V3V4 regions of the 16S rRNA gene of 20 samples from four niches (tongue, buccal mucosa, keratinized gingiva and hard palate) and 10 samples from two life stages (adult and old) were analysed. Flow cytometry (FCM) was used to investigate the resident immune cells. The niche-specialist and age-related communities, characterized based on the microbiota structure, interspecies communications, microbial functions and interactions with immune cells, were addressed. The phylum was the major component in the oral community. The microbial community profiles at the genus level showed that the relative abundances of the genera , and were enriched in the gingiva. The abundance of the genera , and was increased in palatal samples, while the abundance of and was enriched in buccal samples. The genera , and were proportionally enriched in old samples, while and were enriched in adult samples. Network analysis showed that the genus performed as a central node in the buccal module, while in the gingiva module, the central nodes were and . FCM showed that the proportion of Th1 cells in the tongue samples (38.18 % [27.03–49.34 %]) (mean [range]) was the highest. The proportion of γδT cells in the buccal mucosa (25.82 % [22.1–29.54 %]) and gingiva (20.42 % [18.31–22.53 %]) samples was higher (<0.01) than those in the palate (14.18 % [11.69–16.67 %]) and tongue (9.38 % [5.38–13.37 %] samples. The proportion of Th2 (31.3 % [16.16–46.44 %]), Th17 (27.06 % [15.76–38.36 %]) and Treg (29.74 % [15.71–43.77 %]) cells in the old samples was higher than that in the adult samples (<0.01). Further analysis of the interplays between the microbiomes and immune cells indicated that Th1 cells in the adult group, nd Th2, Th17 and Treg cells in the old group were the main immune factors strongly associated with the oral microbiota. For example, Th2, Th17 and Treg cells showed a significantly positive correlation with age-related microorganisms such as , and , while Th1 cells showed a negative correlation. Another positive correlation occurred between Th1 cells and several commensal microbiomes such as , and . Th2, Th17 and Treg cells showed the opposite trend. Together, our findings identify the niche-specialist and age-related characteristics of the oral microbial ecosystem and the potential associations between the microbiomes and the mucosal immune cells, providing critical insights into mucosal microbiology.

Funding
This study was supported by the:
  • National Natural Science Foundations of P. R. China (Award 82101017)
    • Principle Award Recipient: ZhiWang
  • National Natural Science Foundations of P. R. China (Award 81972532)
    • Principle Award Recipient: ZhiWang
  • This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial License.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000811
2022-06-22
2022-07-02
Loading full text...

Full text loading...

/deliver/fulltext/mgen/8/6/mgen000811.html?itemId=/content/journal/mgen/10.1099/mgen.0.000811&mimeType=html&fmt=ahah

References

  1. Zubeidat K, Hovav AH. Shaped by the epithelium - postnatal immune mechanisms of oral homeostasis. Trends Immunol 2021; 42:622–634 [View Article] [PubMed]
    [Google Scholar]
  2. Lin D, Yang L, Wen L, Lu H, Chen Q et al. Crosstalk between the oral microbiota, mucosal immunity, and the epithelial barrier regulates oral mucosal disease pathogenesis. Mucosal Immunol 2021; 14:1247–1258 [View Article] [PubMed]
    [Google Scholar]
  3. Bergmeier LA. Oral Mucosa in Health and Disease, 1st edn. Cham: Springer; 2018 [View Article]
    [Google Scholar]
  4. Koren N, Zubeidat K, Saba Y, Horev Y, Barel O et al. Maturation of the neonatal oral mucosa involves unique epithelium-microbiota interactions. Cell Host Microbe 2021; 29:197–209 [View Article] [PubMed]
    [Google Scholar]
  5. Belibasakis GN. Microbiological changes of the ageing oral cavity. Arch Oral Biol 2018; 96:230–232 [View Article] [PubMed]
    [Google Scholar]
  6. Socransky SS, Manganiello SD. The oral microbiota of man from birth to senility. J Periodontol 1971; 42:485–496 [View Article] [PubMed]
    [Google Scholar]
  7. Mark Welch JL, Dewhirst FE, Borisy GG. Biogeography of the oral microbiome: the site-specialist hypothesis. Annu Rev Microbiol 2019; 73:335–358 [View Article] [PubMed]
    [Google Scholar]
  8. Mark Welch JL, Ramírez-Puebla ST, Borisy GG. Oral microbiome geography: micron-scale habitat and niche. Cell Host Microbe 2020; 28:160–168 [View Article] [PubMed]
    [Google Scholar]
  9. Lloyd-Price J, Mahurkar A, Rahnavard G, Crabtree J, Orvis J et al. Strains, functions and dynamics in the expanded Human Microbiome Project. Nature 2017; 550:61–66 [View Article] [PubMed]
    [Google Scholar]
  10. Libby P. The changing landscape of atherosclerosis. Nature 2021; 592:524–533 [View Article] [PubMed]
    [Google Scholar]
  11. Janney A, Powrie F, Mann EH. Host-microbiota maladaptation in colorectal cancer. Nature 2020; 585:509–517 [View Article] [PubMed]
    [Google Scholar]
  12. Chen YE, Fischbach MA, Belkaid Y. Skin microbiota-host interactions. Nature 2018; 553:427–436 [View Article] [PubMed]
    [Google Scholar]
  13. Simón-Soro A, Tomás I, Cabrera-Rubio R, Catalan MD, Nyvad B et al. Microbial geography of the oral cavity. J Dent Res 2013; 92:616–621 [View Article] [PubMed]
    [Google Scholar]
  14. Eren AM, Borisy GG, Huse SM, Mark Welch JL. Oligotyping analysis of the human oral microbiome. Proc Natl Acad Sci U S A 2014; 111:E2875–84 [View Article] [PubMed]
    [Google Scholar]
  15. Ding R, Liu Y, Yang S, Liu Y, Shi H et al. High-throughput sequencing provides new insights into the roles and implications of core microbiota present in pasteurized milk. Food Res Int 2020; 137:109586 [View Article] [PubMed]
    [Google Scholar]
  16. Tropini C, Earle KA, Huang KC, Sonnenburg JL. The gut microbiome: connecting spatial organization to function. Cell Host Microbe 2017; 21:433–442 [View Article] [PubMed]
    [Google Scholar]
  17. Proctor DM, Relman DA. The landscape ecology and microbiota of the human nose, mouth, and throat. Cell Host Microbe 2017; 21:421–432 [View Article] [PubMed]
    [Google Scholar]
  18. Diaz PI, Valm AM. Microbial interactions in oral communities mediate emergent biofilm properties. J Dent Res 2020; 99:18–25 [View Article] [PubMed]
    [Google Scholar]
  19. Valm AM. The structure of dental plaque microbial communities in the transition from health to dental caries and periodontal disease. J Mol Biol 2019; 431:2957–2969 [View Article] [PubMed]
    [Google Scholar]
  20. Proctor DM, Shelef KM, Gonzalez A, Davis CL, Dethlefsen L et al. Microbial biogeography and ecology of the mouth and implications for periodontal diseases. Periodontol 2000 2020; 82:26–41 [View Article] [PubMed]
    [Google Scholar]
  21. Abubucker S, Segata N, Goll J, Schubert AM, Izard J et al. Metabolic reconstruction for metagenomic data and its application to the human microbiome. PLoS Comput Biol 2012; 8:e1002358 [View Article] [PubMed]
    [Google Scholar]
  22. Yang F, Zeng X, Ning K, Liu K-L, Lo C-C et al. Saliva microbiomes distinguish caries-active from healthy human populations. ISME J 2012; 6:1–10 [View Article] [PubMed]
    [Google Scholar]
  23. Huang S, Li R, Zeng X, He T, Zhao H et al. Predictive modeling of gingivitis severity and susceptibility via oral microbiota. ISME J 2014; 8:1768–1780 [View Article] [PubMed]
    [Google Scholar]
  24. Partridge L, Deelen J, Slagboom PE. Facing up to the global challenges of ageing. Nature 2018; 561:45–56 [View Article] [PubMed]
    [Google Scholar]
  25. Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC et al. From discoveries in ageing research to therapeutics for healthy ageing. Nature 2019; 571:183–192 [View Article] [PubMed]
    [Google Scholar]
  26. Cavalli G, Heard E. Advances in epigenetics link genetics to the environment and disease. Nature 2019; 571:489–499 [View Article] [PubMed]
    [Google Scholar]
  27. Schumacher B, Pothof J, Vijg J, Hoeijmakers JHJ. The central role of DNA damage in the ageing process. Nature 2021; 592:695–703 [View Article] [PubMed]
    [Google Scholar]
  28. Ezzati M, Pearson-Stuttard J, Bennett JE, Mathers CD. Acting on non-communicable diseases in low- and middle-income tropical countries. Nature 2018; 559:507–516 [View Article] [PubMed]
    [Google Scholar]
  29. Pega F, Náfrádi B, Momen NC, Ujita Y, Streicher KN et al. Global, regional, and national burdens of ischemic heart disease and stroke attributable to exposure to long working hours for 194 countries, 2000–2016: A systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury. Environment International 2021; 154:106595 [View Article] [PubMed]
    [Google Scholar]
  30. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG et al. Human gut microbiome viewed across age and geography. Nature 2012; 486:222–227 [View Article] [PubMed]
    [Google Scholar]
  31. Feres M, Teles F, Teles R, Figueiredo LC, Faveri M. The subgingival periodontal microbiota of the aging mouth. Periodontol 2000 2016; 72:30–53 [View Article] [PubMed]
    [Google Scholar]
  32. Ebersole JL, Dawson DA III, Emecen Huja P, Pandruvada S, Basu A et al. Age and Periodontal Health—Immunological View. Curr Oral Health Rep 2018; 5:229–241 [View Article] [PubMed]
    [Google Scholar]
  33. Zemouri C, Ofiteru ID, Jakubovics NS. Future directions for studying resilience of the oral ecosystem. Br Dent J 2020; 229:769–773 [View Article]
    [Google Scholar]
  34. Dutzan N, Konkel JE, Greenwell-Wild T, Moutsopoulos NM. Characterization of the human immune cell network at the gingival barrier. Mucosal Immunol 2016; 9:1163–1172 [View Article]
    [Google Scholar]
  35. Sharawi H, Heyman O, Mizraji G, Horev Y, Laviv A et al. The prevalence of gingival dendritic cell subsets in periodontal patients. J Dent Res 2021; 100:1330–1336 [View Article] [PubMed]
    [Google Scholar]
  36. Gaffen SL, Moutsopoulos NM. Regulation of host-microbe interactions at oral mucosal barriers by type 17 immunity. Sci Immunol 2020; 5:eaau4594 [View Article] [PubMed]
    [Google Scholar]
  37. Hovav AH, Wilharm A, Barel O, Prinz I. Development and function of γδT cells in the oral mucosa. J Dent Res 2020; 99:498–505 [View Article] [PubMed]
    [Google Scholar]
  38. Wu RQ, Zhang DF, Tu E, Chen QM, Chen W. The mucosal immune system in the oral cavity-an orchestra of T cell diversity. Int J Oral Sci 2014; 6:125–132 [View Article] [PubMed]
    [Google Scholar]
  39. Wilharm A, Tabib Y, Nassar M, Reinhardt A, Mizraji G et al. Mutual interplay between IL-17-producing γδT cells and microbiota orchestrates oral mucosal homeostasis. Proc Natl Acad Sci U S A 2019; 116:2652–2661 [View Article] [PubMed]
    [Google Scholar]
  40. Seo GY, Giles DA, Kronenberg M. The role of innate lymphoid cells in response to microbes at mucosal surfaces. Mucosal Immunol 2020; 13:399–412 [View Article] [PubMed]
    [Google Scholar]
  41. Lin QC, Kuypers M, Philpott DJ, Mallevaey T. The dialogue between unconventional T cells and the microbiota. Mucosal Immunol 2020; 13:867–876 [View Article] [PubMed]
    [Google Scholar]
  42. Kayama H, Okumura R, Takeda K. Interaction between the microbiota, epithelia, and immune cells in the intestine. Annu Rev Immunol 2020; 38:23–48 [View Article] [PubMed]
    [Google Scholar]
  43. Domingue JC, Drewes JL, Merlo CA, Housseau F, Sears CL. Host responses to mucosal biofilms in the lung and gut. Mucosal Immunol 2020; 13:413–422 [View Article] [PubMed]
    [Google Scholar]
  44. Van Dyke TE, van Winkelhoff AJ. Infection and inflammatory mechanisms. J Periodontol 2013; 84:S1–7 [View Article] [PubMed]
    [Google Scholar]
  45. Sundberg JP, Berndt A, Sundberg BA, Silva KA, Kennedy V et al. Approaches to investigating complex genetic traits in a large-scale inbred mouse aging study. Vet Pathol 2016; 53:456–467 [View Article] [PubMed]
    [Google Scholar]
  46. Snyder JM, Ward JM, Treuting PM. Cause-of-death analysis in rodent aging studies. Vet Pathol 2016; 53:233–243 [View Article] [PubMed]
    [Google Scholar]
  47. Ward JM, Youssef SA, Treuting PM. Why animals die: an introduction to the pathology of aging. Vet Pathol 2016; 53:229–232 [View Article] [PubMed]
    [Google Scholar]
  48. Ackert-Bicknell CL, Anderson LC, Sheehan S, Hill WG, Chang B et al. Aging research using mouse models. Curr Protoc Mouse Biol 2015; 5:95–133 [View Article] [PubMed]
    [Google Scholar]
  49. Treuting PM, Dintzis SM, Frevert CW, Liggitt HD, Montine KS. Comparative Anatomy and Histology: A Mouse and Human Boston: Atlas Elsevier/Academic Press: Amsterdam; 2012
    [Google Scholar]
  50. Grubb SC, Bult CJ, Bogue MA. Mouse phenome database. Nucleic Acids Res 2014; 42:D825–34 [View Article] [PubMed]
    [Google Scholar]
  51. Flurkey K, Brandvain Y, Klebanov S, Austad SN, Miller RA et al. PohnB6F1: a cross of wild and domestic mice that is a new model of extended female reproductive life span. J Gerontol A Biol Sci Med Sci 2007; 62:1187–1198 [View Article] [PubMed]
    [Google Scholar]
  52. Clausen BE, Jon D. Inflammation, 1st ed. Mainz, Germany: Humana Press; 2017
    [Google Scholar]
  53. Rautava J, Pinnell LJ, Vong L, Akseer N, Assa A et al. Oral microbiome composition changes in mouse models of colitis. J Gastroenterol Hepatol 2015; 30:521–527 [View Article] [PubMed]
    [Google Scholar]
  54. Chen S, Zhou Y, Chen Y, Gu J. fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 2018; 34:i884–i890 [View Article] [PubMed]
    [Google Scholar]
  55. Rognes T, Flouri T, Nichols B, Quince C, Mahé F. VSEARCH: a versatile open source tool for metagenomics. PeerJ 2016; 4:e2584 [View Article] [PubMed]
    [Google Scholar]
  56. Edgar RC. UPARSE: highly accurate OTU sequences from microbial amplicon reads. Nat Methods 2013; 10:996–998 [View Article] [PubMed]
    [Google Scholar]
  57. Davis NM, Proctor DM, Holmes SP, Relman DA, Callahan BJ. Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data. Microbiome 2018; 6:226 [View Article] [PubMed]
    [Google Scholar]
  58. Scott CL, Bain CC, Mowat AM. Isolation and identification of intestinal myeloid cells. Methods Mol Biol 2017; 1559:223–239 [View Article] [PubMed]
    [Google Scholar]
  59. Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R et al. Compartmentalized control of skin immunity by resident commensals. Science 2012; 337:1115–1119 [View Article] [PubMed]
    [Google Scholar]
  60. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 2013; 341:569–573 [View Article] [PubMed]
    [Google Scholar]
  61. Dutzan N, Abusleme L, Bridgeman H, Greenwell-Wild T, Zangerle-Murray T et al. On-going mechanical damage from mastication drives homeostatic Th17 cell responses at the oral barrier. Immunity 2017; 46:133–147 [View Article] [PubMed]
    [Google Scholar]
  62. Tan J, Yi W, Wang Z, Ye C, Tian S et al. TRIM21 negatively regulates Corynebacterium pseudotuberculosis-induced inflammation and is critical for the survival of C. pseudotuberculosis infected C57BL6 mice. Veterinary Microbiology 2021; 261:109209 [View Article] [PubMed]
    [Google Scholar]
  63. Sarhan AT, Bahey-El-Din M, Zaghloul TI. Recombinant Ax21 protein is a promising subunit vaccine candidate against Stenotrophomonas maltophilia in a murine infection model. Vaccine 2021; 39:4471–4480 [View Article] [PubMed]
    [Google Scholar]
  64. Lee HH, Sudhakara P, Desai S, Miranda K, Martinez LR et al. Understanding the Basis of METH Mouth Using a Rodent Model of Methamphetamine Injection, Sugar Consumption, and Streptococcus mutans Infection. mBio 2021; 12:e03534–03520 [View Article] [PubMed]
    [Google Scholar]
  65. Bowen WH. Rodent model in caries research. Odontology 2012; 101:9–14 [View Article] [PubMed]
    [Google Scholar]
  66. Wolfoviz-Zilberman A, Kraitman R, Hazan R, Friedman M, Houri-Haddad Y et al. Phage targeting Streptococcus mutans in vitro and in vivo as a caries-preventive modality. Antibiotics (Basel) 2021; 10:1015 [View Article] [PubMed]
    [Google Scholar]
  67. Polak D, Wilensky A, Shapira L, Halabi A, Goldstein D et al. Mouse model of experimental periodontitis induced by Porphyromonas gingivalis/Fusobacterium nucleatum infection: bone loss and host response. J Clin Periodontol 2009; 36:406–410 [View Article] [PubMed]
    [Google Scholar]
  68. Gao L, Kang M, Zhang MJ, Reza Sailani M, Kuraji R et al. Polymicrobial periodontal disease triggers a wide radius of effect and unique virome. NPJ Biofilms Microbiomes 2020; 6:10 [View Article] [PubMed]
    [Google Scholar]
  69. Krishnamoorthy AL, Lemus AA, Solomon AP, Valm AM, Neelakantan P. Interactions between Candida albicans and Enterococcus faecalis in an organotypic oral epithelial model. Microorganisms 2020; 8:1771 [View Article]
    [Google Scholar]
  70. Shade A, Peter H, Allison SD, Baho DL, Berga M et al. Fundamentals of microbial community resistance and resilience. Front Microbiol 2012; 3:417 [View Article] [PubMed]
    [Google Scholar]
  71. Poudel R, Jumpponen A, Schlatter DC, Paulitz TC, Gardener BBM et al. Microbiome networks: a systems framework for identifying candidate microbial assemblages for disease management. Phytopathology 2016; 106:1083–1096 [View Article] [PubMed]
    [Google Scholar]
  72. Kumar GS. Orban’s Oral Histology and Embryology, 14th Edition. Elsevier: India; 2015
    [Google Scholar]
  73. Moutsopoulos NM, Konkel JE. Tissue-specific immunity at the oral mucosal barrier. Trends Immunol 2018; 39:276–287 [View Article] [PubMed]
    [Google Scholar]
  74. Krishnan S, Prise IE, Wemyss K, Schenck LP, Bridgeman HM et al. Amphiregulin-producing γδ T cells are vital for safeguarding oral barrier immune homeostasis. Proc Natl Acad Sci U S A 2018; 115:10738–10743 [View Article] [PubMed]
    [Google Scholar]
  75. Mayassi T, Ladell K, Gudjonson H, McLaren JE, Shaw DG et al. Chronic inflammation permanently reshapes tissue-resident immunity in celiac disease. Cell 2019; 176:967–981 [View Article] [PubMed]
    [Google Scholar]
  76. Nielsen MM, Witherden DA, Havran WL. γδ T cells in homeostasis and host defence of epithelial barrier tissues. Nat Rev Immunol 2017; 17:733–745 [View Article] [PubMed]
    [Google Scholar]
  77. Dibner RR, Weaver AM, Brock MT, Custer GF, Morrison HG et al. Time outweighs the effect of host developmental stage on microbial community composition. FEMS Microbiol Ecol 2021; 97:fiab102 [View Article] [PubMed]
    [Google Scholar]
  78. Preza D, Olsen I, Willumsen T, Boches SK, Cotton SL et al. Microarray analysis of the microflora of root caries in elderly. Eur J Clin Microbiol Infect Dis 2009; 28:509–517 [View Article] [PubMed]
    [Google Scholar]
  79. Karbalaei M, Keikha M, Yousefi B, Ali-Hassanzadeh M, Eslami M. Contribution of aging oral microbiota in getting neurodegenerative diseases. Rev Med Microbiol 2021; 32:90–94 [View Article]
    [Google Scholar]
  80. Santoro A, Zhao J, Wu L, Carru C, Biagi E et al. Microbiomes other than the gut: inflammaging and age-related diseases. Semin Immunopathol 2020; 42:589–605 [View Article] [PubMed]
    [Google Scholar]
  81. Chen C, Hemme C, Beleno J, Shi ZJ, Ning D et al. Oral microbiota of periodontal health and disease and their changes after nonsurgical periodontal therapy. ISME J 2018; 12:1210–1224 [View Article] [PubMed]
    [Google Scholar]
  82. Mosaddad SA, Tahmasebi E, Yazdanian A, Rezvani MB, Seifalian A et al. Oral microbial biofilms: an update. Eur J Clin Microbiol Infect Dis 2019; 38:2005–2019 [View Article] [PubMed]
    [Google Scholar]
  83. Thompson LA, Chen H. Physiology of aging of older adults: systemic and oral health considerations-2021 update. Dent Clin North Am 2021; 65:275–284 [View Article] [PubMed]
    [Google Scholar]
  84. Freire M, Moustafa A, Harkins DM, Torralba MG, Zhang Y et al. Longitudinal study of oral microbiome variation in twins. Sci Rep 2020; 10:7954 [View Article] [PubMed]
    [Google Scholar]
  85. Peterson CT, Sharma V, Elmén L, Peterson SN. Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota. Clin Exp Immunol 2015; 179:363–377 [View Article] [PubMed]
    [Google Scholar]
  86. Hajishengallis G. Aging and its impact on innate immunity and inflammation: implications for periodontitis. J Oral Biosci 2014; 56:30–37 [View Article] [PubMed]
    [Google Scholar]
  87. Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 2000; 908:244–254 [View Article] [PubMed]
    [Google Scholar]
  88. Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 2014; 69 Suppl 1:S4–9 [View Article] [PubMed]
    [Google Scholar]
  89. Ouyang W, Ranganath SH, Weindel K, Bhattacharya D, Murphy TL et al. Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism. Immunity 1998; 9:745–755 [View Article] [PubMed]
    [Google Scholar]
  90. Pandiyan P, Conti HR, Zheng L, Peterson AC, Mathern DR et al. CD4(+)CD25(+)Foxp3(+) regulatory T cells promote Th17 cells in vitro and enhance host resistance in mouse Candida albicans Th17 cell infection model. Immunity 2011; 34:422–434 [View Article] [PubMed]
    [Google Scholar]
  91. Conti HR, Shen F, Nayyar N, Stocum E, Sun JN et al. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med 2009; 206:299–311 [View Article] [PubMed]
    [Google Scholar]
  92. Allam J-P, Duan Y, Winter J, Stojanovski G, Fronhoffs F et al. Tolerogenic T cells, Th1/Th17 cytokines and TLR2/TLR4 expressing dendritic cells predominate the microenvironment within distinct oral mucosal sites. Allergy 2011; 66:532–539 [View Article] [PubMed]
    [Google Scholar]
  93. Cheng S-C, van de Veerdonk FL, Lenardon M, Stoffels M, Plantinga T et al. The dectin-1/inflammasome pathway is responsible for the induction of protective T-helper 17 responses that discriminate between yeasts and hyphae of Candida albicans. J Leukoc Biol 2011; 90:357–366 [View Article] [PubMed]
    [Google Scholar]
  94. Bhaskaran N, Liu Z, Saravanamuthu SS, Yan C, Hu Y et al. Identification of Casz1 as a Regulatory Protein Controlling T Helper Cell Differentiation, Inflammation, and Immunity. Front Immunol 2018; 9:184 [View Article] [PubMed]
    [Google Scholar]
  95. Zhang YJ, Guo JH, Jia R. Treg: a promising immunotherapeutic target in oral diseases. Front Immunol 2021; 12:667862 [View Article] [PubMed]
    [Google Scholar]
  96. Baruch K, Deczkowska A, David E, Castellano JM, Miller O et al. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function. Science 2014; 346:89–93 [View Article] [PubMed]
    [Google Scholar]
  97. Schwartz M, Peralta Ramos JM, Ben-Yehuda H. A 20-Year Journey from Axonal Injury to Neurodegenerative Diseases and the Prospect of Immunotherapy for Combating Alzheimer’s Disease. J Immunol 2020; 204:243–250 [View Article] [PubMed]
    [Google Scholar]
  98. Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 2011; 477:90–94 [View Article] [PubMed]
    [Google Scholar]
  99. García-Peña C, Álvarez-Cisneros T, Quiroz-Baez R, Friedland RP. Microbiota and Aging. A Review and Commentary. Arch Med Res 2017; 48:681–689 [View Article] [PubMed]
    [Google Scholar]
  100. Spychala MS, Venna VR, Jandzinski M, Doran SJ, Durgan DJ et al. Age-related changes in the gut microbiota influence systemic inflammation and stroke outcome. Ann Neurol 2018; 84:23–36 [View Article] [PubMed]
    [Google Scholar]
  101. Curtis MA. The mouth opens wide onto an additional view of immune development at mucosal borders. Cell Host Microbe 2021; 29:148–149 [View Article] [PubMed]
    [Google Scholar]
  102. Pan M, Wang Q, Liu Y, Xiao N, Niu X et al. Paeonol enhances treatment of fluconazole and amphotericin B against oropharyngeal candidiasis through HIF-1α related IL-17 signaling. Med Mycol 2022; 60:myac011 [View Article] [PubMed]
    [Google Scholar]
  103. Vadovics M, Ho J, Igaz N, Alfoldi R, Rakk D et al. Candida albicans enhances the progression of oral squamous cell carcinoma in vitro and in vivo. mBio 2022; 13:e0314421 [View Article]
    [Google Scholar]
  104. Knight R, Vrbanac A, Taylor BC, Aksenov A, Callewaert C et al. Best practices for analysing microbiomes. Nat Rev Microbiol 2018; 16:410–422 [View Article] [PubMed]
    [Google Scholar]
  105. Shansky RM. Are hormones a “female problem” for animal research?. Science 2019; 364:825–826 [View Article] [PubMed]
    [Google Scholar]
  106. Wald C, Wu C. Of mice and women: the bias in animal models. Science 2010; 327:1571–1572 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000811
Loading
/content/journal/mgen/10.1099/mgen.0.000811
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error