The oral commensal Streptococcus mitis activates the aryl hydrocarbon receptor in human oral epithelial cells

Abstract

A bacterium living in the mouth facilitates oral wound healing by activating a protein involved in immune and inflammatory responses. Stian Engen and colleagues from the University of Oslo in Norway cultured human oral epithelial cells with Streptococcus mitis, a bacterium that colonizes surfaces in healthy peoples’ mouths. Its presence altered the activity of 29 proteins involved in transcribing RNA from DNA. Further analyses were conducted on one of these “transcription factors”, the aryl hydrocarbon receptor, which is known to have a role in immune and inflammatory responses. The researchers found that its activation by S. mitis helps heal oral wounds by stimulating the generation of molecules that attract white blood cells to the area to regulate inflammation. This is followed by the release of a lipid that helps in wound repair.

Keywords

aryl hydrocarbon receptor / commensal / inflammation / oral epithelium / prostaglandin E2 / Streptococcus

References

[1] Lee YK, Mazmanian SK. Has the microbiota played a critical role in the evolution of the adaptive immune system. Science, 2010, 330(6012): 1768-1773.

[2] Teughels W, Kinder Haake S, Sliepen I. Bacteria interfere with A. actinomycetemcomitans colonization. J Dent Res, 2007, 86(7): 611-617.

[3] Buffie CG, Pamer EG. Microbiota-mediated colonization resistance against intestinal pathogens. Nat Rev Immunol, 2013, 13(11): 790-801.

[4] Aas JA, Paster BJ, Stokes LN. Defining the normal bacterial flora of the oral cavity. J Clin Microbiol, 2005, 43(11): 5721-5732.

[5] Dewhirst FE, Chen T, Izard J. The human oral microbiome. J Bacteriol, 2010, 192(19): 5002-5017.

[6] Zaura E, Keijser BJ, Huse SM. Defining the healthy "core microbiome" of oral microbial communities. BMC Microbiol, 2009, 9: 259.

[7] Pearce C, Bowden GH, Evans M. Identification of pioneer viridans streptococci in the oral cavity of human neonates. J Med Microbiol, 1995, 42(1): 67-72.

[8] Kolenbrander PE, London J. Adhere today, here tomorrow: oral bacterial adherence. J Bacteriol, 1993, 175(11): 3247-3252.

[9] Mitchell J. Streptococcus mitis: walking the line between commensalism and pathogenesis. Mol Oral Microbiol, 2011, 26(2): 89-98.

[10] Cole MF, Evans M, Fitzsimmons S. Pioneer oral streptococci produce immunoglobulin A1 protease. Infect Immun, 1994, 62(6): 2165-2168.

[11] Denapaite D, Brückner R, Nuhn M. The genome of Streptococcus mitis B6—what is a commensal. PLoS One, 2010, 5(2): e9426.

[12] Kirchherr JL, Bowden GH, Cole MF. Physiological and serological variation in Streptococcus mitis biovar 1 from the human oral cavity during the first year of life. Arch Oral Biol, 2007, 52(1): 90-99.

[13] Rukke HV, Engen SA, Schenck K. Capsule expression in Streptococcus mitis modulates interaction with oral keratinocytes and alters susceptibility to human antimicrobial peptides. Mol Oral Microbiol, 2016, 31(4): 302-313.

[14] Barouki R, Aggerbeck M, Aggerbeck L. The aryl hydrocarbon receptor system. Drug Metabol Drug Interact, 2012, 27(1): 3-8.

[15] Nguyen LP, Bradfield CA. The search for endogenous activators of the aryl hydrocarbon receptor. Chem Res Toxicol, 2008, 21(1): 102-116.

[16] Vogel CF, Sciullo E, Li W. RelB, a new partner of aryl hydrocarbon receptor-mediated transcription. Mol Endocrinol, 2007, 21(12): 2941-2955.

[17] Nakanishi M, Rosenberg DW. Multifaceted roles of PGE2 in inflammation and cancer. Semin Immunopathol, 2013, 35(2): 123-137.

[18] Awji EG, Chand H, Bruse S. Wood smoke enhances cigarette smoke-induced inflammation by inducing the aryl hydrocarbon receptor repressor in airway epithelial cells. Am J Respir Cell Mol Biol, 2015, 52(3): 377-386.

[19] Squier CA, Finkelstein MW Oral mucosa. In: Nancy A, editor. Ten Cate’s Oral Histology, 7th edn. Missouri: Mosby, Elsevier, 2008: 319.

[20] Barouti N, Mainetti C, Fontao L. Dermatology (Basel), 2015, 230(4): 332-339.

[21] Davarinos NA, Pollenz RS. Aryl hydrocarbon receptor imported into the nucleus following ligand binding is rapidly degraded via the cytosplasmic proteasome following nuclear export. J Biol Chem, 1999, 274(40): 28708-28715.

[22] Di Meglio P, Duarte JH, Ahlfors H. Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions. Immunity, 2014, 40(6): 989-1001.

[23] Chiaro CR, Morales JL, Prabhu KS. Leukotriene A4 metabolites are endogenous ligands for the Ah receptor. Biochemistry, 2008, 47(32): 8445-8455.

[24] Seidel SD, Winters GM, Rogers WJ. Activation of the Ah receptor signaling pathway by prostaglandins. J Biochem Mol Toxicol, 2001, 15(4): 187-196.

[25] Martey CA, Baglole CJ, Gasiewicz TA. The aryl hydrocarbon receptor is a regulator of cigarette smoke induction of the cyclooxygenase and prostaglandin pathways in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol, 2005, 289(3): L391-L399.

[26] Su WH, Cheng MH, Lee WL. Nonsteroidal anti-inflammatory drugs for wounds: pain relief or excessive scar formation. Mediators Inflamm, 2010, 2010: 413238.

[27] Hata AN, Breyer RM. Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. Pharmacol Ther, 2004, 103(2): 147-166.

[28] Kalinski P. Regulation of immune responses by prostaglandin E2. J Immunol, 2012, 188(1): 21-28.

[29] Hessle CC, Andersson B, Wold AE. Gram-negative but not Gram-positive, bacteria elicit strong PGE2 production in human monocytes. Inflammation, 2003, 27(6): 329-332.

[30] Kimmel DW, Rogers LM, Aronoff DM. Prostaglandin E2 regulation of macrophage innate immunity. Chem Res Toxicol, 2016, 29(1): 19-25.

[31] Agard M, Asakrah S, Morici LA. PGE2 suppression of innate immunity during mucosal bacterial infection. Front Cell Infect Microbiol, 2013, 3: 45.

[32] Nguyen NT, Hanieh H, Nakahama T. The roles of aryl hydrocarbon receptor in immune responses. Int Immunol, 2013, 25(6): 335-343.