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Professional phagocytes, such as macrophages, neutrophils and dendritic cells, are uniquely qualified to engulf large ( 0.5 m) particles, including microorganisms. The internalization and subsequent destruction of pathogens are key to the innate immune response, and promote antigen presentation and the development of adaptive immunity. After engulfment, the microorganisms are trapped, together with extracellular fluid, in a vacuole, or phagosome, derived from the plasma membrane. Because the nascent phagosomal membrane and its contents are innocuous, they must undergo a drastic conversion to acquire the microbicidal and degradative features associated with innate immunity. This conversion, known as phagosomal maturation, is accomplished through a strictly choreographed sequence of fusion and fission events that involve defined compartments of the endocytic pathway
(FIG. 1). Effective phagocytosis therefore requires two components: particle internalization and phagosomal maturation.
Although most bacteria are successfully internalized and eliminated by phagocytes, several pathogens have developed survival strategies that interfere with the internalization and/or maturation processes. Prevention and management of the infections caused by such pathogens would obviously benefit from understanding the manner in which they circumvent and often co-opt the immune response. This, in turn, requires detailed knowledge of the basic mechanisms underlying phagocytosis. To this end, we briefly
summarize our current knowledge of phagocytosis and describe salient examples of bacterial species that have evolved distinct strategies to evade killing.
Phagosome formation
The interaction of the microorganism with the phagocyte can be direct, through recognition of pathogen-associated molecules (such as surface carbohydrates, peptidoglycans or lipoproteins) by pattern recognition receptors, or indirect, through mediation by opsonins. Opsonins are host factors, such as immunoglobulin G (IgG), and components of the complement cascade that attach to the pathogen surface, acquiring a conformation that is recognized by phagocytic receptors, such as Fc receptors (FcRs) and complement receptor 3 (CR3)1. The signalling that is triggered by the particle varies depending on the nature of the receptors engaged. The pathway elicited by FcR is best understood. Exposure to multivalent ligands induces clustering of these receptors in the plane of the membrane, initiating phosphorylation of their cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAMs) by Src-family kinases2. ITAM phosphorylation recruits and activates the tyrosine kinase http://www.uniprot.org/uniprot/P43405
Web End =SYK , which in turn phosphorylates various substrates3. The events that follow SYK activation and culminate...