title: Myeloid differentiation primary response gene 88 is required for the resolution of otitis media.
abstract: BACKGROUND
  Signaling defects in the Toll-like receptor (TLR) pathway, such as interleukin-1 receptor-associated kinase 4 deficiency, highlight the prominence of TLR signaling in the defense against bacterial disease. Because myeloid differentiation primary response gene 88 (MyD88) can transduce signals from almost all TLRs, we studied its role in otitis media (OM), the most common upper respiratory tract bacterial infectious disease in young children.
  
  
  METHODS
  The middle ears (MEs) of wild-type (WT) and MyD88(-/-) mice were inoculated with nontypeable Haemophilus influenzae (NTHi). ME infection and inflammation were monitored for 21 days after surgery. Bone marrow-derived macrophages from WT and MyD88(-/-) mice were infected with NTHi in vitro to assess their interaction with bacteria.
  
  
  RESULTS
  In WT mice, MyD88 expression was detected in the ME stroma at baseline. MyD88(-/-) mice displayed prolonged ME mucosal thickening and delayed recruitment of neutrophils and macrophages. Although WT mice cleared NTHi within 5 days, viable NTHi were isolated for up to 21 days in MyD88(-/-) mice. The interaction between macrophages and NTHi was significantly altered in MyD88(-/-) mice.
  
  
  CONCLUSIONS
  In this mouse model, MyD88-mediated signaling was important for clearance of infection and resolution of inflammation in acute OM due to NTHi. The role played by innate signaling in children susceptible to chronic or recurrent OM deserves further study.
authors.affiliation: Department of Pediatrics, Division of Allergy, Immunology, Rheumatology, and Infectious Diseases, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Hernandez
authors.forename: Anke
authors.initials: A
authors.lastname: Leichtle
authors.forename: Kwang
authors.initials: K
authors.lastname: Pak
authors.forename: Joerg
authors.initials: J
authors.lastname: Ebmeyer
authors.forename: Sara
authors.initials: S
authors.lastname: Euteneuer
authors.forename: Marygorret
authors.initials: M
authors.lastname: Obonyo
authors.forename: Donald G
authors.initials: DG
authors.lastname: Guiney
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Webster
authors.forename: David H
authors.initials: DH
authors.lastname: Broide
authors.forename: Allen F
authors.initials: AF
authors.lastname: Ryan
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Wasserman
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D004432:Ear, Middle / Q000378:metabolism / Q000382:microbiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005839:Gentamicins / Q000627:therapeutic use; D006192:Haemophilus Infections / Q000235:genetics / Q000276:immunology*; D006193:Haemophilus influenzae; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics* / Q000378:metabolism; D010033:Otitis Media / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D053594:Myeloid Differentiation Factor 88