IFN-γ and R-848 Dependent Activation of Human Monocyte-Derived Dendritic Cells by <i>Neisseria meningitidis</i> Adhesin A

Mazzon, Cristina; Baldani-Guerra, Barbara; Cecchini, Paola; Kasic, Tihana; Viola, Antonella; Bernard, Marina de; Aricò, Beatrice; Gerosa, Franca; Papini, Emanuele

doi:10.4049/jimmunol.179.6.3904

Cited by 25 publications

(20 citation statements)

References 33 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: 82%

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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mentioning

confidence: 82%

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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“…The TAA protein HA from Avibacterium paragallinarum can protect against infectious coryza (Wang et al 2014b). NadA is capable of promoting dendritic cell maturation and may be used as a self-adjuvant (Mazzon et al 2007). Taken together, these studies suggest that TAAs are immunogenic antigens both in model animals and natural hosts.…”

Section: Potential Applications Of Taasmentioning

confidence: 99%

New findings on the function and potential applications of the trimeric autotransporter adhesin

Qin

Wang

Lei

2015

Antonie van Leeuwenhoek

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Trimeric autotransporter adhesins (TAAs) are located on the surface of many pathogenic Gram-negative bacteria. TAAs belong to the autotransporter protein family and consist of three identical monomers. These obligate homotrimeric proteins are secreted through the bacterial type Vc secretion system and share a common molecular organization that each monomer consists of a N-terminal "passenger" domain and a C-terminal translocation domain. TAAs are important virulence factors that are involved in bacterial life cycle and participate in mediating infection, invasion, dissemination and evasion of host immune responses. TAAs have also proved to be useful for many applications, such as vaccines and disease biomarkers. We here mainly focused on new findings on bio-function and application of TAAs in addition to their common structure and secretion mechanisms.

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IFN-γ and R-848 Dependent Activation of Human Monocyte-Derived Dendritic Cells by Neisseria meningitidis Adhesin A

Cited by 25 publications

References 33 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

New findings on the function and potential applications of the trimeric autotransporter adhesin

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