Predominant role of toll-like receptor 2 versus 4 in Chlamydia pneumoniae-induced activation of dendritic cells

Chlamydia pneumoniae is an obligate intracellular human pathogen causing di seases such as pneumonia, bronchitis, and pharyngitis. Because of its intra cellular replication, cell-mediated immune responses are needed to mediate successful defenses of the host. Because dendritic cells play a central rol e in linking innate immunity and Ag-specific cell-mediated immune responses we asked whether dendritic cells are activated upon contact with C pneumon iae and whether known Toll like receptors (TLR) are involved in this proces s. Here we show that C pneumoniae was taken up by bone marrow-derived murin e dendritic cells. Ingested C pneumoniae appeared to be unable to develop m ature inclusion inside dendritic cells. Furthermore, upon contact with C pn eumoniae dendritic cells were potently stimulated because NF-kappaB was act ivated and translocated to the nucleus, cytokines like IL-12p40 and TNF-alp ha were secreted, and expression of MHC class II molecules, CD40, CD80, and CD86 was up-regulated. Importantly, secretion of cytokines as well as tran slocation of NF-kappaB were dependent on the presence of TLR2 and independe nt from TLR4 with the exception of IL-12p40 secretion, which was attenuated in the absence of either a functional TLR2 or 4. In conclusion, we show he re that recognition of the Gram-negative bacterium C. pneumoniae depends la rgely on TLR2 and only to a minor extent on TLR4.