Heat shock factor 1 protects against lung mycoplasma pneumoniae infection in mice.

Abstract

Heat shock factor 1 (HSF1) is a transcriptional factor that controls the induction of heat shock proteins (e.g. HSP70) in response to stress. Bacterial infections contribute to the pathobiology of chronic lung diseases such as chronic obstructive pulmonary disease and asthma. Whether HSF1 is critical to lung bacterial infection remains unknown. This study is aimed at investigating the impact of HSF1 deficiency on lung Mycoplasma pneumoniae (Mp) infection and elucidating the underlying molecular mechanisms, such as Toll-like receptor 2 (TLR2) signaling. HSF1(-/-) and HSF1(+/+) mice were intranasally infected with Mp or saline and sacrificed 4, 24 and 72 h after treatment. HSF1(-/-) mice had a higher lung Mp load than HSF1(+/+) mice. Mp-induced lung TLR2, nuclear factor-κB and associated inflammation [e.g. keratinocyte-derived chemokine (KC), neutrophils and histopathology] were delayed in HSF1(-/-) mice as compared to HSF1(+/+) mice. HSP70 protein levels in bronchoalveolar lavage fluid of HSF1(-/-) mice were decreased. Furthermore, in response to Mp infection, HSF1(-/-) alveolar macrophages had less TLR2 mRNA expression and KC production than HSF1(+/+) counterparts. Nuclear factor-κB activity and KC production in HSF1(-/-) macrophages could be rescued by addition of exogenous HSP70 protein. These data suggest that HSF1 is necessary to initiate host defense against bacterial infection partly through promoting early TLR2 signaling activation.

• Authors: Fabienne Gally, Maisha N Minor, Sean K Smith, Stephanie R Case, Hong Wei Chu
• Journal: Journal of innate immunity (J Innate Immun) Vol. 4 Issue 1 Pg. 59-68 ( 2012) ISSN: 1662-8128 [Electronic] Switzerland
• PMID: 22042134 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 S. Karger AG, Basel.

Chemical References

• DNA-Binding Proteins
• HSP70 Heat-Shock Proteins
• Heat Shock Transcription Factors
• Hsf1 protein, mouse
• NF-kappa B
• Tlr2 protein, mouse
• Toll-Like Receptor 2
• Transcription Factors

Topics

• Animals
• Bronchoalveolar Lavage
• DNA-Binding Proteins (genetics, immunology)
• HSP70 Heat-Shock Proteins (genetics, immunology, pharmacology)
• Heat Shock Transcription Factors
• Immunity, Innate
• Lung (immunology, microbiology, pathology)
• Macrophages, Alveolar (immunology, microbiology, pathology)
• Mice
• Mice, Knockout
• Mycoplasma pneumoniae (immunology)
• NF-kappa B (genetics, immunology)
• Pneumonia, Mycoplasma (genetics, immunology, microbiology, pathology)
• Signal Transduction (drug effects, genetics, immunology)
• Toll-Like Receptor 2 (genetics, immunology)
• Transcription Factors (genetics, immunology)