REVIEW Neutrophils in innate and adaptive immunity Sébastien Jaillon & Maria Rosaria Galdiero & Davide Del Prete & Marco Antonio Cassatella & Cecilia Garlanda & Alberto Mantovani Received: 13 November 2012 / Accepted: 18 March 2013 / Published online: 4 April 2013 # Springer-Verlag Berlin Heidelberg 2013 Abstract Neutrophils have long been viewed as short-lived cells crucial for the elimination of extracellular pathogens, possessing a limited role in the orchestration of the immune response. This dogma has been challenged by recent lines of evidence demonstrating the expression of an increasing num- ber of cytokines and effector molecules by neutrophils. More- over, in analogy with their “big brother” macrophages, neutrophils integrate the environmental signals and can be polarized towards an antitumoural or protumoural phenotype. Neutrophils are a major source of humoral fluid phase pattern recognition molecules and thus contribute to the humoral arm of innate immunity. Neutrophils cross talk and shape the maturation and effector functions of other leukocytes in a direct or indirect manner, through cell–cell contact or cytokine production, respectively. Therefore, neutrophils are integrated in the activation and regulation of the innate and adaptive immune system and play an important role in the resolution or exacerbation of diverse pathologies, including infections, chronic inflammation, autoimmunity and cancer. Keywords Neutrophils . Innate immunity . Adaptive immunity . Pattern recognition molecule . Inflammation . Cancer Introduction The role played by neutrophils in immunity has long been viewed as restricted to the acute phase of inflammation and to resistance against extracellular pathogens [1–3]. This view is consistent with the phagocytic theory of Metchnikoff who proposed more than 100 years ago that polymorphonuclear leukocytes patrol the bloodstream and migrate to the site of infection to phagocytose microbes. Several studies have recently challenged this dogma and placed the neutrophil as a key effector cell in the orchestration of adaptive immu- nity and in the resolution of inflammatory response [1–3]. Indeed, in addition to their phagocytic activity and the stor- age of a set of lytic enzymes and antimicrobial components in their intracellular granules, neutrophils are induced to express molecules (e.g. cytokines, chemokines) involved in the regulation of innate and adaptive response. Neutrophils have emerged as a major source of humoral pattern recogni- tion molecules (PRMs) that recognise pathogen-associated molecular patterns and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. Neutrophils directly interact with macrophages, dendritic cells, and lympho- cyte subsets and modulate their effector functions. For instance, natural killer (NK) cell functions are impaired during neutropenia, and under steady state, neutrophils are crucial for NK cell development both in human and mouse [4]. Consequently, a bidirectional cross talk occurs between neutrophils and NK cells, which stimulates the production of IFN-γ by NK cells and promotes the sur- vival and activation of neutrophils [5, 6]. In addition, polar- ized T helper (Th) 17 cells and innate IL17-producing cells This article is a contribution to the special issue on Neutrophils – Guest Editors: Paul Hasler and Sinuhe Hahn S. Jaillon : M. R. Galdiero : D. Del Prete : C. Garlanda : A. Mantovani Humanitas Clinical and Research Center, via Manzoni 56, 20089 Rozzano, Milan, Italy M. A. Cassatella Department of Pathology and Diagnostics, University of Verona, 37134 Verona, Italy A. Mantovani (*) Department of Biotechnology and Translational Medicine, University of Milan, Rozzano, Milan 20089, Italy e-mail: Alberto.mantovani@humanitasresearch.it M. R. Galdiero Division of Clinical Immunology and Allergy, University of Naples Federico II, via Pansini, 80131 Naples, Italy Semin Immunopathol (2013) 35:377–394 DOI 10.1007/s00281-013-0374-8