Contents lists available at ScienceDirect Seminars in Immunology journal homepage: www.elsevier.com/locate/ysmim Review Nanoparticles and innate immunity: new perspectives on host defence Diana Boraschi a, ⁎ , Paola Italiani a , Roberto Palomba b , Paolo Decuzzi b , Albert Duschl c , Bengt Fadeel d , S. Moein Moghimi e,f a Institute of Protein Biochemistry, National Research Council, Via Pietro Castellino 111, 80131 Napoli, Italy b Laboratory of Nanotechnology for Precision Medicine, Italian Institute of Technology Foundation, Via Morego 30, 16163 Genova, Italy c Department of Molecular Biology, Paris-Lodron Universität Salzburg, Hellbrunner Strasse 34, 5020 Salzburg, Austria d Nanosafety and Nanomedicine Laboratory, Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, 171 77 Stockholm, Sweden e School of Medicine, Pharmacy and Health, Durham University, Queen's Campus, Stockton-on-Tees TS17 6BH, UK f Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK ARTICLE INFO Keywords: Innate immunity Engineered nanoparticles Inflammation Immunosafety Toxicity Complement ABSTRACT The innate immune system provides the first line of defence against foreign microbes and particulate materials. Engineered nanoparticles can interact with the immune system in many different ways. Nanoparticles may thus elicit inflammation with engagement of neutrophils, macrophages and other effector cells; however, it is im- portant to distinguish between acute and chronic inflammation in order to identify the potential hazards of nanoparticles for human health. Nanoparticles may also interact with and become internalised by dendritic cells, key antigen-presenting cells of the immune system, where a better understanding of these processes could pave the way for improved vaccination strategies. Nanoparticle characteristics such as size, shape and deformability also influence nanoparticle uptake by a plethora of immune cells and subsequent immune responses. Furthermore, the corona of adsorbed biomolecules on nanoparticle surfaces should not be neglected. Complement activation represents a special case of regulated and dynamic corona formation on nanoparticles with important implications in clearance and safety. Additionally, the inadvertent binding of bacterial lipopo- lysaccharide to nanoparticles is important to consider as this may skew the outcome and interpretation of im- munotoxicological studies. Here, we discuss nanoparticle interactions with different cell types and soluble mediators belonging to the innate immune system. 1. Introduction 1.1. Engineered nanoparticles and innate immunity The interaction of engineered nanomaterials (NMs) and nano- particles (NPs) with the immune system and the possible induction of inflammation are of particular interest for two main reasons. First, we need to know more about the interaction of NPs with the immune system for understanding their potential health risks. Second, knowing how the immune system recognises and eliminates NPs will help with designing nanomedical products (e.g., drug delivery systems) not only capable of modulating the immune responses, but also of escaping immune surveillance thereby exerting more effectively their ther- apeutic potential. Thus, in the current safe-by-design approach to na- notechnological and nanomedical products, assessing how NPs interact with the immune defences is a crucial issue in determining NP safety versus hazard for human as well as for environmental health [1–4]. Most of the efforts of immunonanotoxicology have been aimed at the innate immune system, since the innate defence effector cells and humoral factors are the first that come in contact with foreign materials introduced into the body. Innate immune defences are particularly enriched in the tissues at the interface with the external environment http://dx.doi.org/10.1016/j.smim.2017.08.013 Received 7 August 2017; Accepted 22 August 2017 ⁎ Corresponding author. E-mail address: d.boraschi@ibp.cnr.it (D. Boraschi). Abbreviations: CNT, carbon nanotube; DAMP, damage associated molecular pattern; DC, dendritic cell; DPM, discoidal polymeric nanoconstructs; HA-PEI, hyaluronic acid-poly (ethyleneimine); HAMP, homeostasis-altering molecular process; LbL, layer-by-layer; LPS, lipopolysaccharide; MASP, MBL-associated serine protease; MBL, mannose-binding lectin; MPO, myeloperoxidase; MPS, mononuclear phagocyte system; MSV, multistage silicon nanovectors; MWCNT, multi-walled CNT; NAcGlc, N-acetyl-D-glucosamine; GO, graphene oxide; NAMP, nanoparticle-associated molecular pattern; NE, neutrophil elastase; NET, neutrophil extracellular trap; NM, nanomaterial; NP, nanoparticle NK natural killer; NLRC4, NLR family CARD domain-containing protein 4; NLRP3, NOD- LRR- and pyrin domain-containing 3; NOD, nucleotide-binding oligomerisation domain; PAMP, pathogen-associated molecular pattern; PEG, polyethylene glycol; PIM, pulmonary intravascular macrophages; PLGA, poly(lactide-co-glycolide); PM, particulate matter; PMN, polymorphonuclear leukocyte; PRR, pattern recognition receptor; PTX, paclitaxel; RBC, red blood cells; ROS, reactive oxygen species; SPION, superparamagnetic iron oxide nanoparticle; SWCNT, single-walled CNT; TAM, tumour- associated macrophages; TLR, Toll-like receptor; QD, quantum dot; XL-MSN, mesoporous silica NP with XL pores Seminars in Immunology xxx (xxxx) xxx–xxx 1044-5323/ © 2017 Elsevier Ltd. All rights reserved. Please cite this article as: Boraschi, D., Seminars in Immunology (2017), http://dx.doi.org/10.1016/j.smim.2017.08.013