Human Dendritic Cell Culture and Bacterial Infection
Dendritic cells (DC) play a key role in the development of natural immunity to microbes. The DC form a bridge between the innate and adaptive immune system by providing key instructions particularly to antigen naïve T-cells. The interaction of DC with T l
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. Introduction The immune system is constantly under microbial challenge, from both pathogenic and commensal organisms. How the immune system initially responds to these encounters appears to be critical for the induction of a protective immune response. Situated at the center of the immune system is the dendritic cell (DC). DCs are professional antigen-presenting cells that have high phagocytic capacity and act as sentinels and are often located in an immature form in submucosal or subcutaneous compartments. Upon encounter with a microbial stimulus the DC then undergoes a process of maturation, resulting in loss of phagocytic ability coupled with an increase in the expression of molecules involved in antigen
Myron Christodoulides (ed.), Neisseria meningitidis: Advanced Methods and Protocols, Methods in Molecular Biology, vol. 799, DOI 10.1007/978-1-61779-346-2_14, © Springer Science+Business Media, LLC 2012
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presentation and T cell co-stimulation (1). Typically, these mature DCs migrate to secondary lymphoid tissue to initiate the immune response through stimulation of T cells. The initial interaction of DCs with microbial stimuli is critical for shaping the outcome of the primary immune response. This response is mediated through the engagement of pathogen-associated molecular patterns (PAMPs), widely expressed by bacteria, fungi, and viruses, with pattern recognition receptors (PRR) such as tolllike receptors (TLR), NOD-like receptors, C-type lectins, and scavenger receptors (2). The consequence of ligand recognition by these receptors can result in antigen uptake, but also starts signaling mechanisms that drive DC maturation and cytokine production. The profile of cytokine production by DC appears to be crucial for inducing either T helper (Th1 and Th2), T regulatory, and Th17 type immune responses (3, 4). In humans, two DC lineages have so far been described: (1) myeloid DCs and (2) plasmacytoid DCs. Myeloid DCs can be found in either peripheral tissue, secondary lymphoid tissue, or circulating in the blood. Plasmacytoid DCs commonly circulate through the blood into lymph nodes but are rarely found in peripheral tissue. The isolation of human DC subsets can be difficult for a number of reasons: (1) enzymatic and mechanical processes used to isolate DCs from tissues can result in DC activation, (2) DCs in blood are rare, and (3) they are often heterogenous in nature. A major breakthrough in the understanding of human DC biology was made by the development of a method for in vitro generation of monocytederived dendritic cells (MDDC) by Sallusto and Lanzavecchia (5). This process allowed the differentiation of a homogenous population of immature DCs that could be produced in relatively large numbers from human blood and are potent stimulators of naïve T cells (5). DCs can also be generated from CD34+ hematopoietic stem cells following stimulation with GM-CSF and TNF-A, but this method gives rise to a more heterogenous population in a semimature state and requires either the use of umbil
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