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Category: Microbial Genetics and Molecular Biology
Interplay between Myeloid Cells and Humoral Innate Immunity, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555819194/9781555819187_Chap37-1.gif /docserver/preview/fulltext/10.1128/9781555819194/9781555819187_Chap37-2.gifAbstract:
The immune system of mammalians is organized around two components: the innate immunity and the adaptive immunity. Older in terms of evolution, the innate immune system constitutes the first line of defense against microorganisms. This system is supplemented by the adaptive immunity, which is more recent in terms of evolution and provides the basis of immunological memory. Both the adaptive and innate immune systems are composed of a cellular and a humoral arm acting in a complementary and coordinated manner to regulate the innate response.
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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.
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.
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.
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.
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 C. albicans, respectively, triggering complement deposition and phagocytosis of pathogens.
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 C. albicans, respectively, triggering complement deposition and phagocytosis of pathogens.
Expression sites, ligands, and activities of soluble PRMs a
Expression sites, ligands, and activities of soluble PRMs a