A multi-omic analysis reveals a regulatory role of CD180 during the response of macrophages to Borrelia burgdorferi [microarray]

Macrophages are cells of the innate immune system with the ability to phagocytose and induce a global pattern of responses that depend on several signalling pathways. We have determined the biosignature of murine bone marrow-derived macrophages and human blood monocytes using transcriptomics and proteomics approaches. We identified a common pattern of genes transcriptionally regulated that overall indicate that the response to B. burgdorferi involves the interaction of spirochetal antigens with several inflammatory pathways corresponding to primary (triggered by pattern recognition receptors) and secondary (induced by proinflammatory cytokines) responses. We also show that the Toll-like receptor family member, CD180 is downregulated by the stimulation of macrophages, but not monocytes, with the spirochete. Silencing Cd180 results in increased phagocytosis while tempering the production of the proinflammatory cytokine, TNF. Cd180-silenced cells produced increased levels of Itgam and surface CD11b, suggesting that the regulation of CD180 by the spirochete initiates a cascade that increases the CR3-mediated phagocytosis of the bacterium while repressing the consequent inflammatory response. Genome-wide changes in gene expression of normal human monocytes stimulated with Borrelia burgdorferi or left unstimulated were generated by microarray gene expression arrays.