Myeloid differentiation primary response gene 88 is required for the resolution of otitis media.
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.
Hernandez
Michelle
M
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.
Leichtle
Anke
A
Pak
Kwang
K
Ebmeyer
Joerg
J
Euteneuer
Sara
S
Obonyo
Marygorret
M
Guiney
Donald G
DG
Webster
Nicholas J
NJ
Broide
David H
DH
Ryan
Allen F
AF
Wasserman
Stephen I
SI
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*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D053594:Myeloid Differentiation Factor 88