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Chapter 45 : Cellular and Extracellular Defenses against Staphylococcal Infections

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Cellular and Extracellular Defenses against Staphylococcal Infections, Page 1 of 2

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Abstract:

Breaches of the skin and mucosal barriers greatly increase the likelihood of invasive staphylococcal infections, affirming the importance of these peripheral barriers in maintaining a normally asymptomatic host-bacterial relationship. Deficiencies in the mobilization or function of polymorphonuclear leukocytes (PMN) are associated with increased susceptibility to infection by many extracellular bacterial pathogens, including staphylococci. However, more recent studies have revived interest in secretion-based extracellular defenses against staphylococci and other gram-positive bacteria. Secreted antistaphylococcal agents may act alone, providing host defense against bacteria that resist or exceed phagocyte-based defenses, and may also act in concert with resident and mobilized phagocytes to increase antibacterial cytotoxicity of host defenses. In general, the action of PMN at extravascular sites of infection requires a highly regulated series of PMN responses resulting in the directed migration of PMN from blood to sites of infection, sequestration of bacterial prey, and intracellular cytotoxic action. Staphylococcal infections in chronic granulomatous disease (CGD) are overwhelmingly of extravascular nature. This is consistent with the retention of normal clearance function of phagocytes in this disease but also raises the possibility that other mechanisms of host defense against intravascular infections are operative. The acute inflammatory response mobilizes both PMN and extracellular antistaphylococcal activity at the site of bacterial invasion. The chapter focuses on the agents whose mechanism of action against has been most extensively studied. These agents are group IIA phospholipase A2 (PLA2), platelet microbicidal proteins (PMPs) and platelet kinocidins, defensins, and cathelicidins.

Citation: Weiss J, Bayer A, Yeaman M. 2006. Cellular and Extracellular Defenses against Staphylococcal Infections, p 544-559. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch45

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Figures

Image of FIGURE 1
FIGURE 1

Schematic representation of PMN engaged in phagocytosis: attachment and internalization of bacterial prey into the phagocytic vacuole, fusion of cytoplasmic granules with the phagosome to deliver antibacterial peptides and proteins, and mobilization of assembled NADPH oxidase within the phagolysosome. Also indicated are K and H fluxes induced by electrogenic effects of oxidase activation. See text for additional details.

Citation: Weiss J, Bayer A, Yeaman M. 2006. Cellular and Extracellular Defenses against Staphylococcal Infections, p 544-559. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch45
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Image of FIGURE 2
FIGURE 2

Schematic representation of platelets before and after activation. Note changes upon cell activation in cell architecture and surface receptors that facilitate platelet adherence and degranulation. Also note the presence of antimicrobial peptides and proteins (e.g., platelet microbicidal proteins [PMPs], thrombin-induced PMPs [tPMPs], and group IIA PLA2) believed to be stored in the alpha granule. (B) Cross-talk between vascular endothelium, platelets (PLT), and PMN in response to localized infection. Infected endothelium expresses products that either directly (e.g., platelet activating factor [PAF] and interleukin-8 [IL-8]) or indirectly (tissue factor) trigger platelet and PMN recruitment and activation and up-regulate surface receptors for (activated) platelets and PMN. (C) Recruitment, adherence, and activation of platelets and PMN (and endothelium) in juxtaposition to adherent bacteria. Degranulation and activation of respiratory burst in PMN and NO production by endothelium (not shown) lead to localized extracellular mobilization of antimicrobial peptides and proteins and toxic oxygen and nitrogen metabolites. Note that products of platelet degranulation include proteins known (e.g., platelet factor IV) or believed (e.g., tPMPs, PMPs, PLA2) to recruit and/or potentiate antimicrobial functions of PMN. Thus, secreted products may provide mechanisms for extracellular killing of (adherent) bacteria that are refractory to phagocytosis and for enhanced uptake and intracellular destruction of bacteria still susceptible to phagocytosis.

Citation: Weiss J, Bayer A, Yeaman M. 2006. Cellular and Extracellular Defenses against Staphylococcal Infections, p 544-559. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch45
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Image of FIGURE 3
FIGURE 3

Synergy between PMN and extracellular group IIA PLA2 in digestion of phospholipids of during phagocytosis by human PMN. Shown are profiles of metabolically labeled bacterial lipids ( ), resolved by thin-layer chromatography, after incubation for 2 h as indicated. Note that appreciable bacterial phospholipid degradation, at concentration of PLA2 tested, occurs only in combined presence of PLA2 and PMN. Note also substantial conversion of bacterial PG→CL, indicative of a stress response induced shortly after phagocytosis. See text and reference for more details.

Citation: Weiss J, Bayer A, Yeaman M. 2006. Cellular and Extracellular Defenses against Staphylococcal Infections, p 544-559. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch45
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