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Emerg Microbes Infect. 2018 Mar 7;7(1):19. doi: 10.1038/s41426-017-0018-5.

A multi-omic analysis reveals the regulatory role of CD180 during the response of macrophages to Borrelia burgdorferi.

Author information

1
Macrophage and Tick Vaccine Laboratory, CIC bioGUNE, 48160, Derio, Bizkaia, Spain.
2
Genome Analysis Platform, CIC bioGUNE, 48160, Derio, Bizkaia, Spain.
3
Proteomics Platform, CIC bioGUNE, 48160, Derio, Bizkaia, Spain.
4
Carlos III Networked Proteomics Platform (ProteoRed-ISCIII), Universidad Autónoma de Madrid, 28049, Cantoblanco, Madrid, Spain.
5
Universidad del País Vasco/Euskal Herriko Unibertsitatea, 48940, Leioa, Bizkaia, Spain.
6
Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Instituto de Salud Carlos III, 28029, Madrid, Spain.
7
Macrophage and Tick Vaccine Laboratory, CIC bioGUNE, 48160, Derio, Bizkaia, Spain. janguita@cicbiogune.es.
8
Ikerbasque, Basque Foundation for Science, 48011, Bilbao, Bizkaia, Spain. janguita@cicbiogune.es.

Abstract

Macrophages are cells of the innate immune system with the ability to phagocytose and induce a global pattern of responses that depend on several signaling pathways. We have determined the biosignature of murine bone marrow-derived macrophages and human blood monocytes using transcriptomic and proteomic approaches. We identified a common pattern of genes that are transcriptionally regulated and 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 produce increased levels of Itgam and surface CD11b, suggesting that the regulation of CD180 by the spirochete initiates a cascade that increases CR3-mediated phagocytosis of the bacterium while repressing the consequent inflammatory response.

PMID:
29511161
PMCID:
PMC5841238
DOI:
10.1038/s41426-017-0018-5
[Indexed for MEDLINE]
Free PMC Article

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