Decreased Expression of TLR-9 and Cytokines in the Presence of Bacteria in Patients with Otitis Media with Effusion
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Objectives. Toll-like receptor (TLR)-9 recognizes unmethylated cytidine-phosphate-guanosine (CpG) motifs in bacteria. Therefore, the expression of TLR-9 may differ according to the results of bacterial culture, and thus a change in proinflammatory cytokine induction can also be expected. The authors aimed to assess the differences and relationships between the expression of TLR-9, cytokines, and nitric oxide synthase (NOS) in otitis media with effusion (OME) based on bacterial culture results. Methods. Sixty-eight patients with OME were divided into culture-positive and culture-negative groups based on middle ear culture results. mRNA expression of TLR-9, NOS, and cytokines was measured and analyzed. Results. Bacteria were detected in 38.2% of patients, and the distribution was as follows: coagulase negative Staphylococcus (10.3%), Staphylococcus aureus (8.8%), Streptococcus pneumonia (5.9%), and Bacillus spp. and Haemophilus influenza combined (2.9%). There were no significant differences in epidemiologic characteristics according to the culture results. Down-regulation of TLR-9 was observed in the culture-positive group (P=0.019). Cytokines including interleukin (IL)-12 (r=-0.582), tumor necrosis factor (TNF)-α (r=-0.569), interferon (IFN)-γ (r=-0.442), IL-6 (r=-0.395) and inducible NOS (r=-0.256) tended to decrease with the detection of bacteria. Conclusion. The expression of TLR-9 significantly decreased in OME with confirmed bacterial pathogens. IL-12, TNF-α, IFN-β, IL-6 expression tended to decrease with the detection of bacteria. The presence of bacterial pathogens in OME may be related to abnormalities in the innate immune system.
Abstract
Objectives. Toll-like receptor (TLR)-9 recognizes unmethylated cytidine-phosphate-guanosine (CpG) motifs in bacteria. Therefore, the expression of TLR-9 may differ according to the results of bacterial culture, and thus a change in proinflammatory cytokine induction can also be expected. The authors aimed to assess the differences and relationships between the expression of TLR-9, cytokines, and nitric oxide synthase (NOS) in otitis media with effusion (OME) based on bacterial culture results. Methods. Sixty-eight patients with OME were divided into culture-positive and culture-negative groups based on middle ear culture results. mRNA expression of TLR-9, NOS, and cytokines was measured and analyzed. Results. Bacteria were detected in 38.2% of patients, and the distribution was as follows: coagulase negative Staphylococcus (10.3%), Staphylococcus aureus (8.8%), Streptococcus pneumonia (5.9%), and Bacillus spp. and Haemophilus influenza combined (2.9%). There were no significant differences in epidemiologic characteristics according to the culture results. Down-regulation of TLR-9 was observed in the culture-positive group (P=0.019). Cytokines including interleukin (IL)-12 (r=-0.582), tumor necrosis factor (TNF)-α (r=-0.569), interferon (IFN)-γ (r=-0.442), IL-6 (r=-0.395) and inducible NOS (r=-0.256) tended to decrease with the detection of bacteria. Conclusion. The expression of TLR-9 significantly decreased in OME with confirmed bacterial pathogens. IL-12, TNF-α, IFN-β, IL-6 expression tended to decrease with the detection of bacteria. The presence of bacterial pathogens in OME may be related to abnormalities in the innate immune system.
참고문헌 (26)
- American Academy of Family Physicians, "Otitis media with effusion", Pediatrics, 113(5), pp.1412~1429 (2004)
- Hurst DS, "The role of allergy in otitis media with effusion", Otolaryngol Clin North Am, 44(3), pp.637~654 (2011)
- Alper CM, "Temporal relationships for cold-like illnesses and otitis media in sibling pairs", Pediatr Infect Dis J, 26(9), pp.778~781 (2007)
- Leichtle A, "Innate signaling in otitis media: pathogenesis and recovery", Curr Allergy Asthma Rep, 11(1), pp.78~84 (2011)
- Casey JR, "Changes in frequency and pathogens causing acute otitis media in 1995-2003", Pediatr Infect Dis J, 23(9), pp.824~828 (2004)
- Howie VM, "Immunoglobulins of the middle ear fluid in acute otitis media: relationship to serum immunoglobulin concentrations and bacterial cultures", Infect Immun, 7(4), pp.589~593 (1973)
- Yeo SG, "Relationship between effusion bacteria and concentrations of immunoglobulin in serum and effusion fluid in otitis media with effusion patients", Int J Pediatr Otorhinolaryngol, 72(3), pp.337~342 (2008)
- Ryan AF, "The effect of complement depletion on immunologically mediated middle ear effusion and inflammation", Clin Immunol Immunopathol, 40(3), pp.410~421 (1986)
- Kim MG, "TLR-9, NOD-1, NOD-2, RIG-I and immunoglobulins in recurrent otitis media with effusion", Int J Pediatr Otorhinolaryngol, 74(12), pp.1425~1429 (2010)
- Ozcan E, "Toll-like receptor 9, transmembrane activator and calcium-modulating cyclophilin ligand interactor, and CD40 synergize in causing B-cell activation", J Allergy Clin Immunol, 128(3), pp.601~609 (2011)
- Leichtle A, "The role of DNA sensing and innate immune receptor TLR9 in otitis media", Innate Immun, 18(1), pp.3~13 (2012)
- Daniel M, "Bacterial involvement in otitis media with effusion", Int J Pediatr Otorhinolaryngol, 76(10), pp.1416~1422 (2012)
- Huebner J, "Coagulase-negative staphylococci: role as pathogens", Annu Rev Med, 50, pp.223~236 (1999)
- Paluch-Oles J, "The phenotypic and genetic biofilm formation characteristics of coagulase-negative staphylococci isolates in children with otitis media", Int J Pediatr Otorhinolaryngol, 75(1), pp.126~130 (2011)
- Palm NW, "Pattern recognition receptors and control of adaptive immunity", Immunol Rev, 227(1), pp.221~233 (2009)
- Kawai T, "The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors", Nat Immunol, 11(5), pp.373~384 (2010)
- Leichtle A, "TLR4-mediated induction of TLR2 signaling is critical in the pathogenesis and resolution of otitis media", Innate Immun, 15(4), pp.205~215 (2009)
- Parra MM, "Bacterial etiology and serotypes of acute otitis media in Mexican children", Vaccine, 29(33), pp.5544~5549 (2011)
- McGillivary G, "Respiratory syncytial virus-induced dysregulation of expression of a mucosal beta-defensin augments colonization of the upper airway by non-typeable Haemophilus influenzae", Cell Microbiol, 11(9), pp.1399~1408 (2009)
- Granath A, "Altered Toll- and Nod-like receptor expression in human middle ear mucosa from patients with chronic middle ear disease", J Infect, 63(2), pp.174~176 (2011)
- Kariya S, "TH1", TH2 and regulatory cytokines in adults with otitis media with effusion, 2006, pp.27(8), 1089~1093
- Beutler B, "Inferences, questions and possibilities in Toll-like receptor signalling", Nature, 430(6996), pp.257~263 (2004)
- Thoma-Uszynski S, "Induction of direct antimicrobial activity through mammalian toll-like receptors", Science, 291(5508), pp.1544~1547 (2001)
- Conboy PJ, "The nose and nitric oxide: a review", Clin Otolaryngol Allied Sci, 25(5), pp.337~341 (2000)
- Kleinert H, "Regulation of the expression of inducible nitric oxide synthase", Biol Chem, 384(10-11), pp.1343~1364 (2003)
- Xu Q, "Identification of Streptococcus pneumoniae and Haemophilus influenzae in culture-negative middle ear fluids from children with acute otitis media by combination of multiplex PCR and multi-locus sequencing typing", Int J Pediatr Otorhinolaryngol, 75(2), pp.239~244 (2011)