The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells

Chorny, Alejo; Casas-Recasens, Sandra; Sintes, Jordi; Shan, Meimei; Polentarutti, Nadia; García‐Escudero, Ramón; Walland, A; Yeiser, John R.; Cassis, Linda; Carrillo, Jorge; Puga, Irene; Cunha, Cristina; Bastos, Hélder Novais; Rodrigues, Fernando; Lacerda, João F.; Morais, António; Dieguez-Gonzalez, Rebeca; Heeger, Peter S.; Salvatori, Giovanni; Carvalho, Agostinho; Garcı́a-Sastre, Adolfo; Blander, J. Magarian; Mantovani, Alberto; Garlanda, Cecília; Cerutti, Andrea

doi:10.1084/jem.20150282

Cited by 74 publications

(89 citation statements)

References 45 publications

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“…Perhaps neutrophils in rhesus macaques reach full maturation at another anatomical site. Several studies have provided evidence for this to occur in mice (34, 35). …”

Section: Resultsmentioning

confidence: 98%

Neutrophil progenitor populations of rhesus macaques

Weisgrau

Vosler

Pomplun

et al. 2018

Journal of Leukocyte Biology

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Captive-bred rhesus macaques of Indian origin represent one of the most important large animal models for infectious disease, solid organ transplantation and stem cell research. There is a dearth of information defining hematopoietic development, including neutrophil leukocyte differentiation in this species using multicolor flow cytometry. In the current study we sought to identify cell surface markers that delineate neutrophil progenitor populations with characteristic immunophenotypes. We defined four different post-mitotic populations based on their CD11b and CD87 expression pattern, and further refined their immunophenotypes using CD32, CD64, lactoferrin and myeloperoxidase as antigenic markers. The four subsets contained myelocyte, metamyelocyte, band, and segmented neutrophil populations. We compared our flow cytometry-based classification with the classical nuclear morphology-based classification. We found overlap of immunological phenotype between populations of different nuclear morphology and identified phenotypically different subsets within populations of similar nuclear morphology. We assessed the responsiveness of these populations to stimulatory signals such as LPS, fMPL or PMA, and demonstrated significant differences between human and rhesus macaque neutrophil progenitors. In this study we provided evidence for species-specific features of granulopoiesis that ultimately manifested in the divergent immunophenotypes of the fully differentiated segmented neutrophils of humans and rhesus macaques. Additionally, we found functional markers that can be used to accurately quantify neutrophil progenitors by flow cytometry. While these markers do not coincide with the classical nuclear-morphology-based grading they enable us to perform functional studies monitoring immunophenotypic markers.

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“…Perhaps neutrophils in rhesus macaques reach full maturation at another anatomical site. Several studies have provided evidence for this to occur in mice (34, 35). …”

Section: Resultsmentioning

confidence: 98%

Neutrophil progenitor populations of rhesus macaques

Weisgrau

Vosler

Pomplun

et al. 2018

Journal of Leukocyte Biology

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“…Based on present knowledge, it may serve as a key factor of humoral innate immunity2728293031. New information indicates that it serves as an endogenous adjuvant for B-cells, at least in spleen32. PTX3 is being discussed as a potential biomarker for infectious diseases, as it is detectable in the circulation2930.…”

Section: Discussionmentioning

confidence: 99%

Sterile inflammation as a factor in human male infertility: Involvement of Toll like receptor 2, biglycan and peritubular cells

Mayer¹,

Adam

Glashauser³

et al. 2016

Sci Rep

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Changes in the wall of seminiferous tubules in men with impaired spermatogenesis imply sterile inflammation of the testis. We tested the hypothesis that the cells forming the wall of seminiferous tubules, human testicular peritubular cells (HTPCs), orchestrate inflammatory events and that Toll like receptors (TLRs) and danger signals from the extracellular matrix (ECM) of this wall are involved. In cultured HTPCs we detected TLRs, including TLR2. A TLR-2 ligand (PAM) augmented interleukin 6 (IL-6), monocyte chemo-attractant protein-1 (MCP-1) and pentraxin 3 (PTX3) in HTPCs. The ECM-derived proteoglycan biglycan (BGN) is secreted by HTPCs and may be a TLR2-ligand at HTPCs. In support, recombinant human BGN increased PTX3, MCP-1 and IL-6 in HTPCs. Variable endogenous BGN levels in HTPCs derived from different men and differences in BGN levels in the tubular wall in infertile men were observed. In testes of a systemic mouse model for male infertility, testicular sterile inflammation and elevated estradiol (E2) levels, BGN was also elevated. Hence we studied the role of E2 in HTPCs and observed that E2 elevated the levels of BGN. The anti-estrogen ICI 182,780 blocked this action. We conclude that TLR2 and BGN contribute to sterile inflammation and infertility in man.

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“…Broadly, PRRs are located within the cell cytosol, embedded in the cell membrane, or secreted extracellularly. Soluble extracellular PRRs include members of the complement system and the pentraxins that bind to phosphocholine in both a calcium dependent and independent manner [1, 2]. Membrane-associated receptors include the Toll-like receptor (TLR) and C-type lectin receptor (CLR) families, whereas cytosolic receptors include the Nod-like receptor (NLR), Rig-I-like helicase (RLR), and AIM2-like receptor (ALR) families (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Modulating inflammation through the negative regulation of NF-κB signaling

Rothschild

McDaniel

Ringel‐Scaia

et al. 2018

Journal of Leukocyte Biology

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Immune system activation is essential to thwart the invasion of pathogens and respond appropriately to tissue damage. However, uncontrolled inflammation can result in extensive collateral damage underlying a diverse range of auto-inflammatory, hyper-inflammatory, and neoplastic diseases. The NF-κB signaling pathway lies at the heart of the immune system and functions as a master regulator of gene transcription. Thus, this signaling cascade is heavily targeted by mechanisms designed to attenuate overzealous inflammation and promote resolution. Mechanisms associated with the negative regulation of NF-κB signaling are currently under intense investigation and have yet to be fully elucidated. Here, we provide an overview of mechanisms that negatively regulate NF-κB signaling through either attenuation of signal transduction, inhibition of posttranscriptional signaling, or interference with posttranslational modifications of key pathway components. While the regulators discussed for each group are far from comprehensive, they exemplify common mechanistic approaches that inhibit this critical biochemical signaling cascade. Despite their diversity, a commonality among these regulators is their selection of specific targets at key inflection points in the pathway, such as TNF-receptor-associated factor family members or essential kinases. A better understanding of these negative regulatory mechanisms will be essential to gain greater insight related to the maintenance of immune system homeostasis and inflammation resolution. These processes are vital elements of disease pathology and have important implications for targeted therapeutic strategies.

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The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells

Abstract: Cerutti and collaborators show that the humoral arms of the innate and adaptive immune systems are functionally interconnected by pentraxin 3, a soluble pattern recognition receptor that couples innate immune recognition with antibody-inducing function.

Cited by 74 publications

References 45 publications

Neutrophil progenitor populations of rhesus macaques

Neutrophil progenitor populations of rhesus macaques

Sterile inflammation as a factor in human male infertility: Involvement of Toll like receptor 2, biglycan and peritubular cells

Modulating inflammation through the negative regulation of NF-κB signaling

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