Airway epithelial MyD88 restores control of Pseudomonas aeruginosa murine infection via an IL-1-dependent pathway.

Abstract

The opportunistic human pathogen Pseudomonas aeruginosa causes rapidly progressive and tissue-destructive infections, such as hospital-acquired and ventilator-associated pneumonias. Innate immune responses are critical in controlling P. aeruginosa in the mammalian lung, as demonstrated by the increased susceptibility of MyD88(-/-) mice to this pathogen. Experiments conducted using bone marrow chimeric mice demonstrated that radio-resistant cells participated in initiating MyD88-dependent innate immune responses to P. aeruginosa. In this study we used a novel transgenic mouse model to demonstrate that MyD88 expression by epithelial cells is sufficient to generate a rapid and protective innate immune response following intranasal infection with P. aeruginosa. MyD88 functions as an adaptor for many TLRs. However, mice in which multiple TLR pathways (e.g., TLR2/TLR4/TLR5) are blocked are not as compromised in their response to P. aeruginosa as mice lacking MyD88. We demonstrate that IL-1R signaling is an essential element of MyD88-dependent epithelial cell responses to P. aeruginosa infection.

• Authors: Lilia A Mijares, Tamding Wangdi, Caroline Sokol, Robert Homer, Ruslan Medzhitov, Barbara I Kazmierczak
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 186 Issue 12 Pg. 7080-8 (Jun 15 2011) ISSN: 1550-6606 [Electronic] United States
• PMID: 21572023 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1
• Myd88 protein, mouse
• Myeloid Differentiation Factor 88

Topics

• Animals
• Humans
• Immunity, Innate
• Interleukin-1 (metabolism)
• Mice
• Mice, Knockout
• Myeloid Differentiation Factor 88 (immunology)
• Pseudomonas Infections (immunology)
• Pseudomonas aeruginosa (immunology)
• Respiratory Mucosa (immunology, microbiology)
• Signal Transduction (immunology)