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-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.
Rodríguez
Nuria
N
Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.
Mages
Jörg
J
Dietrich
Harald
H
Wantia
Nina
N
Wagner
Hermann
H
Lang
Roland
R
Miethke
Thomas
T
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002690:Chlamydia Infections / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D016993:Chlamydophila pneumoniae / Q000302:isolation & purification*; D017931:DNA Primers; D008168:Lung / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger