Monocytes and Macrophages
Monocytes and macrophages are essential for the development of inflammation and together with neutrophils are the phagocytic cells involved in the clearance of inert particles and microbial agents. Monocytes are bone marrow-derived cells that are continuously released into the blood. When these cells are recruited by chemotactic molecules, and leave circulation, they become activated and differentiate into macrophages under the stimulus of mediators such as TGF-β or M-CSF, between others (Gordon and Martínez 2009). Macrophages have a number of important functions in body defenses such as (1) capture by phagocytosis and intracellular killing of microorganisms; (2) scavenging of debris potentially harmful to tissues; (3) processing and presentation of antigens for recognition by T cells, and (4) releasing cytokines and chemokines with a major role in immune responses (Davies et al. 2013). The major cytokines produced by macrophages are TNF-α, IL-1β, IL-6, IL-8 and IL-33, all of which are involved in local and systemic responses. Macrophages demonstrate great developmental plasticity and may differentiate into cells with different phenotypes depending on the stimuli received as well as the tissue location. IFN-γ induces classically activated M1 macrophages (CAM), whereas IL-4, IL-13 and IL-10 induce alternatively activated M2-macrophages (AAM) (Mosser and Edwards 2008). In the intestinal mucosa M2-macrophages are more abundant, participating in the resolution of parasite infections, tissue remodeling, immune regulation, allergy development and tumor progression by stimulating a Th2-driven immune response (Takeuchi and Akira 2011). Chapter 14 describes in detail the main characteristics and differentiation protocols for THP-1 and U937, two human monocytic cells lines commonly employed in the study of the anti-inflammatory properties of food bioactives. The main food components tested, together with the methods employed to evaluate their potential anti-inflammatory activity are also explained.
Dendritic cells (DC) are a widely distributed group of cells specialized in antigen sampling. In fact, they also constitute the most efficient antigen presenting cells for T cell activation, hence being the linking bridge between innate and adaptive immune responses. DCs are strategically positioned at body barriers and also organ entry ports, such as the splenic marginal zone, where they remain in an immature form until they encounter an antigen (Mildner and Jung 2014). Once the antigen has been sampled, DCs become activated and travel towards T-cell zones, either within their respective lymphoid organ of residence or towards draining lymph nodes to ensure the activation, proliferation and differentiation of naïve T cells into their corresponding effector cells. This migration depends on the expression of the chemokine receptor CCR7 (Foster et al. 1999). During migration, the mature dendritic cells express high surface levels of class II major histocompatibility complex (MHC) molecules with bound antigenic peptides as well as costimulatory molecules. By the time DCs reach secondary lymphoid organs, they are able to present antigens to populations of naïve and memory T cells. Chapter 17 provides a complete overview of the different DC subsets focusing on the DCs present in the intestinal mucosa as they are among the first immune cells to come into contact with food compounds in the gastrointestinal tract and thus are instrumental in shaping the immune system's response to such exposures. In the same chapter the main DC isolation techniques as well as in vitro/ex vivo culture settings that can be applied for in vitro testing of food compounds with bioactive properties are discussed. Special attention will be paid to the potential of food-derived bioactives in inhibiting DC activation due to the relevance of DCs in initiating the inflammatory processes.