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.

• MeSH
• aktivace makrofágů imunologie   MeSH
• Borrelia burgdorferi imunologie   MeSH
• cytokiny metabolismus   MeSH
• fagocytóza imunologie   MeSH
• lymeská nemoc imunologie   metabolismus   mikrobiologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• proteomika MeSH
• receptory buněčného povrchu imunologie   metabolismus   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Species of Scedosporium and Lomentospora are considered as emerging opportunists, affecting immunosuppressed and otherwise debilitated patients, although classically they are known from causing trauma-associated infections in healthy individuals. Clinical manifestations range from local infection to pulmonary colonization and severe invasive disease, in which mortality rates may be over 80%. These unacceptably high rates are due to the clinical status of patients, diagnostic difficulties, and to intrinsic antifungal resistance of these fungi. In consequence, several consortia have been founded to increase research efforts on these orphan fungi. The current review presents recent findings and summarizes the most relevant points, including the Scedosporium/Lomentospora taxonomy, environmental distribution, epidemiology, pathology, virulence factors, immunology, diagnostic methods, and therapeutic strategies.

• MeSH
• antifungální látky farmakologie   terapeutické užití   MeSH
• Ascomycota klasifikace   účinky léků   genetika   fyziologie   MeSH
• chirurgie operační MeSH
• ekologie MeSH
• faktory virulence MeSH
• imunokompromitovaný pacient MeSH
• interakce hostitele a patogenu imunologie   MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• mnohočetná fungální léková rezistence genetika   MeSH
• molekulární typizace MeSH
• mykózy diagnóza   mikrobiologie   patologie   terapie   MeSH
• oportunní infekce diagnóza   mikrobiologie   patologie   terapie   MeSH
• Scedosporium klasifikace   účinky léků   genetika   fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH