MyD88-dependent changes in the pulmonary transcriptome after infection with Chlamydia pneumoniae.
Physiol Genomics
; 30(2): 134-45, 2007 Jul 18.
Article
em En
| MEDLINE
| ID: mdl-17374847
Chlamydia pneumoniae, an intracellular bacterium, causes pneumonia in humans and mice. Toll-like receptors and the key adaptor molecule myeloid differentiation factor-88 (MyD88) play a critical role in inducing immunity against this microorganism and are crucial for survival. To explore the influence of MyD88 on induction of immune responses in vivo on a genome-wide level, wildtype (WT) or MyD88(-/-) mice were infected with C. pneumoniae on anesthesia, and the pulmonary transcriptome was analyzed 3 days later by microarrays. We found that the infection caused pulmonary cellular infiltration in WT but not MyD88(-/-) mice. Furthermore, it induced the transcription of 360 genes and repressed 18 genes in WT mice. Of these, 221 genes were not or weakly induced in lungs of MyD88(-/-) mice. This cluster contains primarily genes encoding for chemokines and cytokines like MIP-1alpha, MIP-2, MIP-1gamma, MCP-1, TNF, and KC and other immune effector molecules like immunoresponsive gene-1 and TLR2. Arginase was highly induced after C. pneumoniae infection and was MyD88 dependent. Genes induced by interferons were abundant in a cluster of 102 genes that were only partially MyD88 dependent. Also, lcn2 (lipocalin-2) and timp1 were represented within this cluster. Interestingly, a set of 37 genes including sprr1a was induced more strongly in MyD88(-/-) mice, and most of them are involved in the regulation of cellular replication. In summary, ex vivo analysis of the pulmonary transcriptome on infection with C. pneumoniae demonstrated a major impact of MyD88 on inflammatory responses but not on interferon-type responses and identified MyD88-independent genes involved in cellular replication.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
Infecções por Chlamydia
/
Chlamydophila pneumoniae
/
Fator 88 de Diferenciação Mieloide
/
Pulmão
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Physiol Genomics
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Alemanha