The membrane expression of <i>Neisseria meningitidis</i> adhesin A (NadA) increases the proimmune effects of <i>MenB</i> OMVs on human macrophages, compared with NadA– OMVs, without further stimulating their proinflammatory activity on circulating monocytes

Tavano, Regina; Franzoso, Susanna; Cecchini, Paola; Cartocci, Elena; Oriente, Francesca; Aricò, Beatrice; Papini, Emanuele

doi:10.1189/jlb.0109030

Cited by 47 publications

(34 citation statements)

References 21 publications

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“…Recent studies have shown that NadA is involved in interaction with and stimulation of immune cells during infection (2)(3)(4) and in binding to the human chaperone Hsp90 (5,6). Its predicted molecular structure is very similar to the known virulence-associated factors Yersinia adhesin A (YadA) and UspA2 (7,8), which suggests that NadA is a member of the OCA (oligomeric coiled-coil adhesin) family (9).…”

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confidence: 81%

Neisseria Adhesin A Variation and Revised Nomenclature Scheme

Bambini¹,

Chiara²,

Muzzi³

et al. 2014

Clin. Vaccine Immunol.

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c Neisseria adhesin A (NadA), involved in the adhesion and invasion of Neisseria meningitidis into host tissues, is one of the major components of Bexsero, a novel multicomponent vaccine licensed for protection against meningococcal serogroup B in Europe, Australia, and Canada. NadA has been identified in approximately 30% of clinical isolates and in a much lower proportion of carrier isolates. Three protein variants were originally identified in invasive meningococci and named NadA-1, NadA-2, and NadA-3, whereas most carrier isolates either lacked the gene or harbored a different variant, NadA-4. Further analysis of isolates belonging to the sequence type 213 (ST-213) clonal complex identified NadA-5, which was structurally similar to NadA-4, but more distantly related to NadA-1, -2, and -3. At the time of this writing, more than 89 distinct nadA allele sequences and 43 distinct peptides have been described. Here, we present a revised nomenclature system, taking into account the complete data set, which is compatible with previous classification schemes and is expandable. The main features of this new scheme include (i) the grouping of the previously named NadA-2 and NadA-3 variants into a single NadA-2/3 variant, (ii) the grouping of the previously assigned NadA-4 and NadA-5 variants into a single NadA-4/5 variant, (iii) the introduction of an additional variant (NadA-6), and (iv) the classification of the variants into two main groups, named groups I and II. To facilitate querying of the sequences and submission of new allele sequences, the nucleotide and amino acid sequences are available at http://pubmlst.org/neisseria/NadA/.

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confidence: 81%

Neisseria Adhesin A Variation and Revised Nomenclature Scheme

Bambini¹,

Chiara²,

Muzzi³

et al. 2014

Clin. Vaccine Immunol.

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“…Its adhesive role is important in the course of colonization of the human upper respiratory tract (10,35). Following the passage across the epithelium, meningococcus invades tissues and blood, where NadA can interact with human blood leukocytes and lead to enhanced immune stimulation (36)(37)(38)(39). For these reasons, NadA is to be considered an important meningococcal virulence factor, involved in progressively invasive steps of infection.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Regulation of the nadA Gene in Neisseria meningitidis Impacts the Prediction of Coverage of a Multicomponent Meningococcal Serogroup B Vaccine

et al. 2013

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bThe NadA adhesin is a major component of 4CMenB, a novel vaccine to prevent meningococcus serogroup B (MenB) infection. Under in vitro growth conditions, nadA is repressed by the regulator NadR and poorly expressed, resulting in inefficient killing of MenB strains by anti-NadA antibodies. Interestingly, sera from children infected with strains that express low levels of NadA in laboratory growth nevertheless recognize the NadA antigen, suggesting that NadA expression during infection may be different from that observed in vitro. In a strain panel covering a range of NadA levels, repression was relieved through deleting nadR. All nadR knockout strains expressed high levels of NadA and were efficiently killed by sera from subjects immunized with 4CMenB. A selected MenB strain, NGP165, mismatched for other vaccine antigens, is not killed by sera from immunized infants when the strain is grown in vitro. However, in an in vivo passive protection model, the same sera effectively protected infant rats from bacteremia with NGP165. Furthermore, we identify a novel hydroxyphenylacetic acid (HPA) derivative, reported by others to be produced during inflammation, which induces expression of NadA in vitro, leading to efficient antibody-mediated killing. Finally, using bioluminescent reporters, nadA expression in the infant rat model was induced in vivo at 3 h postinfection. Our results suggest that during infectious disease, NadR repression is alleviated due to niche-specific signals, resulting in high levels of NadA expression from any nadA-positive (nadA ؉ ) strain and therefore efficient killing by anti-NadA antibodies elicited by the 4CMenB vaccine.

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“…Serum samples were analyzed with a suspension array system (Bio-Plex; Bio-Rad, Hercules, Calif., USA) for the quantification of 9 cytokines [IL-1α, -1β, -2, -4, -6 and -10, interferon-γ (IFN-γ) and TNF-α] following the manufacturer's instructions as previously described [14,15,17]. …”

Section: Methodsmentioning

confidence: 99%

The Role of Congestion in Cardiorenal Syndrome Type 2: New Pathophysiological Insights into an Experimental Model of Heart Failure

et al. 2015

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Background: In cardiorenal syndrome type 2 (CRS2), the role of systemic congestion in heart failure (HF) is still obscure. We studied a model of CRS2 [monocrotaline (MCT)-treated rats] secondary to pulmonary hypertension and right ventricular (RV) failure in order to evaluate the contribution of prevalent congestion to the development of kidney injury. Methods: Ten animals were treated with MCT for 4 weeks until they developed HF. Eleven animals were taken as controls. Signs of hypertrophy and dilatation of the right ventricle demonstrated the occurrence of HF. Brain natriuretic peptide (BNP), serum creatinine (sCreatinine), both kidney and heart neutrophil gelatinase-associated lipocalin (NGAL), matrix metallopeptidase 9 (MMP9), serum cytokines as well as kidney and heart cell death, as assessed by TUNEL, were studied. Results: Rats with HF showed higher BNP levels [chronic HF (CHF) 4.8 ± 0.5 ng/ml; controls 1.5 ± 0.2 ng/ml; p < 0.0001], marked RV hypertrophy and dilatation (RV mass/RV volume: CHF 1.46 ± 0.31, controls 2.41 ± 0.81; p < 0.01) as well as pleural and peritoneal effusions. A significant increase in proinflammatory cytokines and sCreatinine was observed (CHF 3.06 ± 1.3 pg/ml vs. controls 0.54 ± 0.23 pg/ml; p = 0.04). Serum (CHF 562.7 ± 93.34 ng/ml vs. controls 245.3 ± 58.19 ng/ml; p = 0.02) as well as renal and heart tissue NGAL levels [CHF 70,680 ± 4,337 arbitrary units (AU) vs. controls 32,120 ± 4,961 AU; p = 0.001] rose significantly, and they were found to be complexed with MMP9 in CHF rats. A higher number of kidney TUNEL-positive tubular cells was also detected (CHF 114.01 ± 45.93 vs. controls 16.36 ± 11.60 cells/mm²; p = 0.0004). Conclusion: In this model of CHF with prevalent congestion, kidney injury is characterized by tubular damage and systemic inflammation. The upregulated NGAL complexed with MMP9 perpetuates the vicious circle of kidney/heart damage by enhancing the enzymatic activity of MMP9 with extracellular matrix degradation, worsening heart remodeling.

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The membrane expression of Neisseria meningitidis adhesin A (NadA) increases the proimmune effects of MenB OMVs on human macrophages, compared with NadA– OMVs, without further stimulating their proinflammatory activity on circulating monocytes

Cited by 47 publications

References 21 publications

Neisseria Adhesin A Variation and Revised Nomenclature Scheme

Neisseria Adhesin A Variation and Revised Nomenclature Scheme

Transcriptional Regulation of the nadA Gene in Neisseria meningitidis Impacts the Prediction of Coverage of a Multicomponent Meningococcal Serogroup B Vaccine

The Role of Congestion in Cardiorenal Syndrome Type 2: New Pathophysiological Insights into an Experimental Model of Heart Failure

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