The Interleukin-1β/CXCL1/2/Neutrophil Axis Mediates Host Protection against Group B Streptococcal Infection

Biondo, Carmelo; Mancuso, Giuseppe; Midiri, Angelina; Signorino, Giacomo; Domina, Maria; Cariccio, Veronica Lanza; Mohammadi, Nastaran Keshavarz; Venza, Mario; Teti, Giuseppe; Beninati, Concetta

doi:10.1128/iai.02104-14

Cited by 79 publications

(102 citation statements)

References 40 publications

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“…Both of these organisms trigger IL-1␤ secretion through toxin-dependent activation of the inflammasome (36,37), which drives neutrophil activation and proinflammatory cytokine production that controls infection (38,39). The contribution of inflammasome signaling during natural carriage of these organisms remains unexplored.…”

Section: Discussionmentioning

confidence: 99%

Sensing of Interleukin-1 Cytokines during Streptococcus pneumoniae Colonization Contributes to Macrophage Recruitment and Bacterial Clearance

2015

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Streptococcus pneumoniae (the pneumococcus), a leading cause of bacterial disease, is most commonly carried in the human nasopharynx. Colonization induces inflammation that promotes the organism's growth and transmission. This inflammatory response is dependent on intracellular sensing of bacterial components that access the cytosolic compartment via the pneumococcal pore-forming toxin pneumolysin. In vitro, cytosolic access results in cell death that includes release of the proinflammatory cytokine interleukin-1␤ (IL-1␤). IL-1 family cytokines, including IL-1␤, are secreted upon activation of inflammasomes, although the role of this activation in the host immune response to pneumococcal carriage is unknown. Using a murine model of pneumococcal nasopharyngeal colonization, we show that mice deficient in the interleukin-1 receptor type 1 (Il1r1 ؊/؊ ) have reduced numbers of neutrophils early after infection, fewer macrophages later in carriage, and prolonged bacterial colonization. Moreover, intranasal administration of Il-1␤ promoted clearance. Macrophages are the effectors of clearance, and characterization of macrophage chemokines in colonized mice revealed that Il1r1 ؊/؊ mice have lower expression of the C-C motif chemokine ligand 6 (CCL6), correlating with reduced macrophage recruitment to the nasopharynx. IL-1 family cytokines are known to promote adaptive immunity; however, we observed no difference in the development of humoral or cellular immunity to pneumococcal colonization between wild-type and Il1r1 ؊/؊ mice. Our findings show that sensing of IL-1 cytokines during colonization promotes inflammation without immunity, which may ultimately benefit the pneumococcus. Streptococcus pneumoniae (the pneumococcus) is an opportunistic bacterial pathogen that is responsible for over 1 million deaths annually, mostly in children under the age of 5 years (1). The pneumococcus serially colonizes the mucosal surfaces of the human upper respiratory tract, and carriage of the organism provides the reservoir for all pneumococcal disease (2). Colonization induces airway inflammation that is characterized by a suppurative rhinitis and increased mucus secretion. These secretions promote bacterial growth (3), and inflammation is important for bacterial transmission in a viral coinfection model (4). Human studies have demonstrated that higher bacterial burdens are correlated with a more profound rhinitis (5); however, as a result of this inflammatory response, colonization is normally cleared by the host's immune system within several weeks (6).A well-defined murine model of pneumococcal colonization (7) has elucidated bacterial and host factors that are critical to immune recognition of the pneumococcus, which drives the eventual resolution of the carrier state. Although early colonization triggers the recruitment of neutrophils, these are ineffective at resolving the infection. Clearance of pneumococci from the upper airway over a period of weeks requires a sustained presence of macrophages in the nasopharynx (8). Althou...

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Section: Discussionmentioning

confidence: 99%

Sensing of Interleukin-1 Cytokines during Streptococcus pneumoniae Colonization Contributes to Macrophage Recruitment and Bacterial Clearance

2015

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“…bacterial) where it functions locally as an alarmin (125–130). IL-1β is induced during infection and is primarily produced by monocytes, macrophages and dendritic cells (131–134). IL-1 signals through the IL-1R1 receptor present on a number of cells including endothelial cells, monocytes, macrophages and T lymphocytes (116, 128, 135, 136).…”

Section: Cytokinesmentioning

confidence: 99%

Cytokines and Chemokines inMycobacterium tuberculosisInfection

et al. 2016

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Chemokines and cytokines are critical for initiating and coordinating the organized and sequential recruitment and activation of cells into Mycobacterium tuberculosis -infected lungs. Correct mononuclear cellular recruitment and localization are essential to ensure control of bacterial growth without the development of diffuse and damaging granulocytic inflammation. An important block to our understanding of TB pathogenesis lies in dissecting the critical aspects of the cytokine/chemokine interplay in light of the conditional role these molecules play throughout infection and disease development. Much of the data highlighted in this review appears at first glance to be contradictory, but it is the balance between the cytokines and chemokines that is critical, and the “goldilocks” (not too much and not too little) phenomenon is paramount in any discussion of the role of these molecules in TB. Determination of how the key chemokines/cytokines and their receptors are balanced and how the loss of that balance can promote disease is vital to understanding TB pathogenesis and to identifying novel therapies for effective eradication of this disease.

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“…It has been showed that IL‐1β deficient mice have defective systemic and local neutrophil mobilization (Biondo et al, ). C‐X‐C motif ligand 1 (CXCL1) has been shown to promote neutrophil migration (Biondo et al, ). As we previously reported, rapid release of IL‐1β and CXCL1, and the migration of neutrophils into the wound site was seen in the CM.…”

Section: Resultsmentioning

confidence: 99%

MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions

et al. 2016

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Our previous studies have shown that Dexamethasone (Dex) reduced the expression of matrix-metalloproteinases (MMPs -1,-3,-9,-13), IL-1β and IL-6, while it significantly increased MMP-8 mRNA transcripts in a concomitant dry eye and corneal alkali burn murine model (CM). To investigate if MMP-8 induction is responsible for some of the protective effects of Dex in CM, MMP-8 knock out mice (MMP-8KO) were subjected to the CM for 2 or 5 days and topically treated either with 2 μl of 0.1% Dexamethasone (Dex), or saline QID. A separate group of C57BL/6 mice were topically treated with Dex or BSS and received either 100 nM CAM12 (MMP-8 inhibitor) or vehicle IP, QD. Here we demonstrate that topical Dex treated MMP-8KO mice subjected to CM showed reduced corneal clarity, increased expression of inflammatory mediators (IL-6, CXCL1, and MMP-1 mRNA) and increased neutrophil infiltration at 2D and 5D compared to Dex treated WT mice. C57BL/6 mice topically treated with Dex and CAM12 IP recapitulated findings seen with MMP-8KO mice. These results suggest that some of the anti-inflammatory effects of Dex are mediated through increased MMP-8 expression.

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The Interleukin-1β/CXCL1/2/Neutrophil Axis Mediates Host Protection against Group B Streptococcal Infection

Cited by 79 publications

References 40 publications

Sensing of Interleukin-1 Cytokines during Streptococcus pneumoniae Colonization Contributes to Macrophage Recruitment and Bacterial Clearance

Sensing of Interleukin-1 Cytokines during Streptococcus pneumoniae Colonization Contributes to Macrophage Recruitment and Bacterial Clearance

Cytokines and Chemokines inMycobacterium tuberculosisInfection

MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions

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