Regulation of macrophage activity by surface receptors contained within Borrelia burgdorferi-enriched phagosomal fractions

English version

Autoři: Ana Carreras-González ^aff001; Diego Barriales ^aff001; Ainhoa Palacios ^aff001; Marta Montesinos-Robledo ^aff001; Nicolás Navasa ^aff001; Mikel Azkargorta ^aff002; Ainize Peña-Cearra ^aff001; Julen Tomás-Cortázar ^aff001; Iraide Escobes ^aff002; Miguel Angel Pascual-Itoiz ^aff001; Jana Hradiská ^aff003; Jan Kopecký ^aff003; David Gil-Carton ^aff004; Rafael Prados-Rosales ^aff001; Leticia Abecia ^aff001; Estíbaliz Atondo ^aff001; Itziar Martín ^aff001; Aize Pellón ^aff001; Félix Elortza ^aff002; Héctor Rodríguez ^aff001; Juan Anguita ^aff001
Působiště autorů: Inflammation and Macrophage Plasticity Laboratory, CIC bioGUNE, Derio, Bizkaia, Spain ^aff001; Proteomics Platform, CIBERehd, ProteoRed-ISCIII, CIC bioGUNE, Derio, Bizkaia, Spain ^aff002; Faculty of Science, University of South Bohemia, Branišovská, České Budějovice, Czech Republic ^aff003; Structural Biology Unit, CIC bioGUNE, Derio, Bizkaia, Spain ^aff004; Ikerbasque, Basque Foundation for Science, Bilbao, Bizkaia, Spain ^aff005
Vyšlo v časopise: Regulation of macrophage activity by surface receptors contained within Borrelia burgdorferi-enriched phagosomal fractions. PLoS Pathog 15(11): e32767. doi:10.1371/journal.ppat.1008163
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008163

Souhrn

Macrophages mediate the elimination of pathogens by phagocytosis resulting in the activation of specific signaling pathways that lead to the production of cytokines, chemokines and other factors. Borrelia burgdorferi, the causative agent of Lyme disease, causes a wide variety of pro-inflammatory symptoms. The proinflammatory capacity of macrophages is intimately related to the internalization of the spirochete. However, most receptors mediating this process are largely unknown. We have applied a multiomic approach, including the proteomic analysis of B. burgdorferi-containing phagosome-enriched fractions, to identify surface receptors that are involved in the phagocytic capacity of macrophages as well as their inflammatory output. Sucrose gradient protein fractions of human monocyte-derived macrophages exposed to B. burgdorferi contained the phagocytic receptor, CR3/CD14 highlighting the major role played by these proteins in spirochetal phagocytosis. Other proteins identified in these fractions include C-type lectins, scavenger receptors or Siglecs, of which some are directly involved in the interaction with the spirochete. We also identified the Fc gamma receptor pathway, including the binding receptor, CD64, as involved both in the phagocytosis of, and TNF induction in response to B. burgdorferi in the absence of antibodies. The common gamma chain, FcγR, mediates the phagocytosis of the spirochete, likely through Fc receptors and C-type lectins, in a process that involves Syk activation. Overall, these findings highlight the complex array of receptors involved in the phagocytic response of macrophages to B. burgdorferi.

Klíčová slova:

Borrelia burgdorferi – Cell binding – Macrophages – Phagocytosis – Fc receptors – Spirochetes – Phagosomes – Complement receptors

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