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Interplay between Myeloid Cells and Humoral Innate Immunity

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  • Authors: Sébastien Jaillon1,2, Eduardo Bonavita*3,4, Cecilia Garlanda5,6, Alberto Mantovani7,8
  • Editor: Siamon Gordon9
    Affiliations: 1: Humanitas Clinical Research Center; 2: Humanitas University, 20089, Rozzano (Milano), Italy; 3: Humanitas Clinical Research Center; 4: *Present address: Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4QL, United Kingdom.; 5: Humanitas Clinical Research Center; 6: Humanitas University, 20089, Rozzano (Milano), Italy; 7: Humanitas Clinical Research Center; 8: Humanitas University, 20089, Rozzano (Milano), Italy; 9: Oxford University, Oxford, United Kingdom
  • Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0051-2016
  • Received 04 October 2016 Accepted 04 October 2016 Published 16 December 2016
  • Alberto Mantovani, [email protected]
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  • Abstract:

    The innate immune system represents the first line of defense against pathogens and comprises both a cellular and a humoral arm. Fluid-phase pattern recognition molecules (PRMs), which include collectins, ficolins, and pentraxins, are key components of the humoral arm of innate immunity and are expressed by a variety of cells, including myeloid, epithelial, and endothelial cells, mainly in response to infectious and inflammatory conditions. Soluble PRMs share basic multifunctional properties including activation and regulation of the complement cascade, opsonization of pathogens and apoptotic cells, regulation of leukocyte extravasation, and fine-tuning of inflammation. Therefore, soluble PRMs are part of the immune response and retain antibody-like effector functions. Here, we will review the expression and general function of soluble PRMs, focusing our attention on the long pentraxin PTX3.

  • Citation: Jaillon S, Bonavita* E, Garlanda C, Mantovani A. 2016. Interplay between Myeloid Cells and Humoral Innate Immunity. Microbiol Spectrum 4(6):MCHD-0051-2016. doi:10.1128/microbiolspec.MCHD-0051-2016.


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The innate immune system represents the first line of defense against pathogens and comprises both a cellular and a humoral arm. Fluid-phase pattern recognition molecules (PRMs), which include collectins, ficolins, and pentraxins, are key components of the humoral arm of innate immunity and are expressed by a variety of cells, including myeloid, epithelial, and endothelial cells, mainly in response to infectious and inflammatory conditions. Soluble PRMs share basic multifunctional properties including activation and regulation of the complement cascade, opsonization of pathogens and apoptotic cells, regulation of leukocyte extravasation, and fine-tuning of inflammation. Therefore, soluble PRMs are part of the immune response and retain antibody-like effector functions. Here, we will review the expression and general function of soluble PRMs, focusing our attention on the long pentraxin PTX3.

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Humoral innate immunity. Soluble PRMs are expressed and secreted by a variety of cells, including in particular myeloid cells, allowing the production of PRMs over time. Some PRMs (e.g., PTX3, PGRP-S, and ficolin-1) are stored in neutrophil granules for rapid release in minutes. PRMs such as PTX3 and PGRP-S are also found among NET-associated molecules (NAMs). Production of PRMs by mononuclear phagocytes, dendritic cells, and endothelium in a gene expression-dependent manner sustains the presence of these molecules over time. Finally, epithelial tissues (e.g., liver) sustain systemic mass production.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0051-2016
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Gene organization, protein structures, and roles of PTX3. The PTX3 gene is organized in three exons. The first two exons code for the signal peptide (SP) and the N-terminal domain of the protein (NTD), respectively, and the third exon codes for the pentraxin domain (PTX). A three-dimensional model of the pentraxin domain has been generated based on the crystallographic structures of CRP and SAP, showing that the pentraxin domain of PTX3 adopts a β-jelly roll topology. PTX3 has a unique quaternary structure with eight subunits, associated together to form an octamer by disulfide bonds between cysteine residues present on both the N-terminal and C-terminal domains. Once released, PTX3 plays a role in pathogen opsonization and agglutination, complement activation, regulation of inflammation and leukocyte recruitment, angiogenesis, extracellular matrix (ECM) remodeling, and wound healing. Men B, meningococcus type B; FGF, fibroblast growth factor 2; TSG-6, tumor necrosis factor-inducible gene 6 protein; IαI, inter-alpha-trypsin inhibitor.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0051-2016
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Role of PTX3 in defense against fungi. In the presence of PTX3-opsonized conidia, FcγRIIA induces inside-out CD11b/CD18 activation, recruitment to the phagocytic cup, and amplification of C3b-opsonized conidia phagocytosis (left panel). PTX3 interacts with ficolin-2 and MBL on the surface of conidia and , respectively, triggering complement deposition and phagocytosis of pathogens.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0051-2016
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Expression sites, ligands, and activities of soluble PRMs

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0051-2016

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