Cytotoxic Necrotizing Factor 1 Downregulates CD36 Transcription in Macrophages to Induce Inflammation During Acute Urinary Tract Infections

Autor: Huan Yang, Qianqian Li, Changying Wang, Jingyu Wang, Junqiang Lv, Lei Wang, Zhi-Song Zhang, Zhi Yao, Quan Wang
Rok vydání: 2017
Předmět:
0301 basic medicine
lcsh:Immunologic diseases. Allergy
CD36 Antigens
Immunology
Bacterial Toxins
Down-Regulation
Inflammation
urologic and male genital diseases
Microbiology
Apoptotic cell clearance
Pathogenesis
03 medical and health sciences
Mice
Downregulation and upregulation
medicine
Immunology and Allergy
Animals
Homeostasis
Humans
Uropathogenic Escherichia coli
Scavenger receptor
cdc42 GTP-Binding Protein
Transcription factor
Cells
Cultured
Escherichia coli Infections
Liver X Receptors
Kidney
Innate immune system
Pyelonephritis
business.industry
Escherichia coli Proteins
cytotoxic necrotizing factor 1
Immunity
Innate
macrophages
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Acute Disease
Urinary Tract Infections
Macrophages
Peritoneal
Female
medicine.symptom
business
CD36
lcsh:RC581-607
Zdroj: Frontiers in Immunology, Vol 9 (2018)
ISSN: 1664-3224
Popis: Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) induce cystitis, pyelonephritis, and can cause kidney scarring and failure if inflammation is not under control. The detailed effects of cytotoxic necrotizing factor 1 (CNF1), the key UPEC toxin, on the pathogenicity of UPEC remain unclear. CD36 is an important scavenger receptor, responsible for pathogen and apoptotic cell clearance, and plays an essential role in host immune defense and homeostasis. Regulation of CD36 by bacterial toxins has not been reported. In this study, using a pyelonephritis mouse model, CNF1 was observed to contribute to increasing neutrophils and bacterial titers in infected bladder and kidney tissues, resulting in severe inflammation and tissue damage. CD36 expression in macrophages was found to be decreased by CNF1 in vitro and in vivo. We demonstrated that CNF1 attenuated CD36 transcription by decreasing expressions of its upstream transcription factors LXRβ and C/EBPα and their recruitment to the CD36 promotor. In addition, Cdc42 was found to be involved in CNF1-mediated downregulation of LXRβ. Our study investigated the pathogenesis of cnf1-carrying UPEC, which affected host innate immune defenses and homeostasis through regulation of CD36 in macrophages during acute UTIs.
Databáze: OpenAIRE
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