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Macrophage responses to bacterial toxins: a balance between activation and suppression

  • University of Pittsburgh Immunology 2011
  • Published:
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Abstract

Toxins secreted by bacteria can impact the host in a number of different ways. In some infections, toxins play a crucial and central role in pathogenesis (i.e., anthrax), while in other bacterial infections, the role of toxins is less understood. The cholesterol-dependent cytolysins (CDCs), of which streptolysin O is a prototype, are a class of pore-forming toxins produced by many gram-positive bacteria and have only been studied in a few experimental infection models. Our laboratory has demonstrated that CDCs have effects on macrophages that are both pro- and anti-inflammatory. Here, we review evidence that CDCs promote inflammation by driving secretion of IL-1β and HMGB-1 from macrophages in a NLRP3-dependent manner, while also causing shedding of membrane microvesicles from cells that can interact with macrophages and inhibit TNF-α release. CDCs thus impact macrophage function in ways that may be both beneficial and detrimental to the host.

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Acknowledgments

We thank members of the Salter lab for helpful discussion. This work was supported by NIH grants AI072083 and CA073743. PAK is supported by training grant T32CA82084, and MEH is supported by training grant T32AI089443.

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Authors and Affiliations

  1. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA

    Peter A. Keyel, Michelle E. Heid & Russell D. Salter

  2. Immunology Graduate Program, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA

    Michelle E. Heid

  3. E1052 BST, 200 Lothrop St, Pittsburgh, PA, 15261, USA

    Russell D. Salter

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  1. Peter A. Keyel
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  2. Michelle E. Heid
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  3. Russell D. Salter
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Correspondence to Russell D. Salter.

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Keyel, P.A., Heid, M.E. & Salter, R.D. Macrophage responses to bacterial toxins: a balance between activation and suppression. Immunol Res 50, 118–123 (2011). https://doi.org/10.1007/s12026-011-8212-3

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  • DOI: https://doi.org/10.1007/s12026-011-8212-3

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