Gold nanoparticles attenuates bacterial sepsis in cecal ligation and puncture mouse model through the induction of M2 macrophage polarization

BMC Microbiology

Thunnicha Ondee¹  Saowapha Surawut²  Amornpun Sereemaspun³  Naunpun Sangphech⁴  Sujittra Taratummarat⁵  Tanapat Palaga⁶  Chau Tran Bao Vu⁷ 

[1] Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;Department of Microbiology and Immunology and Research Unit of Oral Microbiology, Chulalongkorn University, Bangkok, Thailand;Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand;Medical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand;Medical Sciences Program, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;Oral Biology program, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand

关键词: Sepsis;    Gold nanoparticles;    Cecal ligation and puncture;    Macrophage polarization;   

DOI  :  10.1186/s12866-018-1227-3

学科分类：微生物学和免疫学

来源: BioMed Central

【 摘 要 】

Gold nanoparticles (AuNP) have several biochemical advantageous properties especially for a candidate of drug carrier. However, the non-conjugated AuNP has a higher rate of cellular uptake than the conjugated ones. Spherical AuNP in a proper size (20–30 nm) is non-toxic to mice and shows anti-inflammatory properties. We tested if the administration of AuNP, as an adjuvant to antibiotics, could attenuate bacterial sepsis in cecal ligation and puncture (CLP) mouse model with antibiotic (imipenem/cilastatin). Indeed, AuNP administration at the time of CLP improved the survival, blood bacterial burdens, kidney function, liver injury and inflammatory cytokines (TNF-α, IL-6, IL-1β and IL-10). AuNP also decreased M1 macrophages (CD86 + ve in F4/80 + ve cells) and increased M2 macrophages (CD206 + ve in F4/80 + ve cells) in the spleens of sepsis mice. The weak antibiotic effect of AuNP was demonstrated as the reduction of E. coli colony after 4 h incubation. In addition, AuNP altered cytokine production of bone-marrow-derived macrophages including reduced TNF-α, IL-6 and IL-1β but increased IL-10 at 6 and 24 h. Moreover, AuNP induced macrophage polarization toward anti-inflammatory responses (M2) as presented by increased Arg1 (Arginase 1) and PPARγ with decreased Nos2 (inducible nitric oxide synthase, iNos) and Nur77 at 3 h after incubation in vitro. The adjuvant therapy of AuNP, with a proper antibiotic, attenuated CLP-induced bacterial sepsis in mice, at least in part, through the antibiotic effect and the induction of macrophage function toward the anti-inflammatory responses.

【 授权许可】

CC BY