MyD88-dependent changes in the pulmonary transcriptome after infection with Chlamydia pneumoniae

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- 1 alpha, MIP- 2, MIP- 1 gamma, 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 sprrla 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-independentgenes involved in cellular replication.