Characterisation of an experimental mouse model of exposure to nanoparticles. Relevance to human sarcoidosis

Background: Nanoparticles are increasingly suspected as a strong etiologic factor in sarcoidosis pathogenesis.The aim of our study was to evaluate lung inflammatory response and histology changes following exposure of mice to two types of nanoparticles: carbon nanotubes (MWCNT) and cadmium-based nanoparticles (QDOT705) in order to better our understanding of human sarcoidosis. Material and methods: Various groups of mice were included: control mice received PBS or Complete Freund9s adjuvant, and mice that received PBS or Complete Freund9s adjuvant were intranasally exposed to QDOTs or MWCNT. One month later, blood and bronchoalveolar lavages (BAL) were collected for cell counts and cytokine profile and lung tissues processed for histology and immunostaining studies. Results: We observed: 1) higher BAL cellularity compared to controls; 2) increased numbers of neutrophils, macrophages and lymphocytes; 3) high CXCL9 and CXCL10 levels; 3) heterogeneous areas with increased cellular infiltrates and granuloma surfaces; 4) CD3+ T and B cells cells infiltration in inflammatory areas; 4) up-regulated mediators: CXCL2, CCR1 and IL6 (inflammatory cell recruitment); CCR5 (TH1 recruitment and maturation); IL6 and IL23A (TH17 maturation); CXCL15 and IL13 (bronchial cell activation and hyper-reactivity); TLR2 and TLR9 (innate immunity). Of relevance, these mouse data correlate with those observed in human sarcoidosis. Conclusions: our mouse model describes the initial inflammatory and histological processes in response to nanoparticles that mimics “pre-granulomatous“ lesions and mediator production, which are important steps in paving the way for sarcoidosis development in humans.