Outer membrane protein A of Acinetobacter baumannii induces differentiation of CD4+ T cells toward a Th1 polarizing phenotype through the activation of dendritic cells

Lee, Jun Sik; Lee, Je Chul; Lee, Chang-Min; Jung, In Duk; Jeong, Young-Il; Seong, Eun-Young; Chung, Ho Young; Park, Yeong‐Min

doi:10.1016/j.bcp.2007.02.012

Cited by 63 publications

(60 citation statements)

References 29 publications

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“…This isogenic derivative harbors a transposon insertion within a gene coding for a product that has the same predicted amino acid sequence (GenBank accession number AY485227) reported for A. baumannii 19606 outer membrane protein 38 (11). Although that report was the first to provide evidence for the apoptotic role of this protein, that work and subsequent publications from the same research group (10,19,24,25) did not provide experimental evidence supporting the role of this outer membrane protein in the ability of A. baumannii to interact with abiotic and biotic surfaces. Thus, the data presented in this report indicate that although not essential, as it is in the case of CsuA/BABCDE pili (45), OmpA is needed for the formation of robust biofilms on polystyrene.…”

Section: Discussionmentioning

confidence: 88%

The Acinetobacter baumannii 19606 OmpA Protein Plays a Role in Biofilm Formation on Abiotic Surfaces and in the Interaction of This Pathogen with Eukaryotic Cells

2009

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The ability of Acinetobacter baumannii to adhere to and persist on surfaces as biofilms could be central to its pathogenicity. The production of pili and a biofilm-associated protein and the expression of antibiotic resistance are needed for robust biofilm formation on abiotic and biotic surfaces. This multistep process also depends on the expression of transcriptional regulatory functions, some of which could sense nutrients available to cells. This report extends previous observations by showing that although outer membrane protein A (OmpA) of A. baumannii 19606 plays a partial role in the development of robust biofilms on plastic, it is essential for bacterial attachment to Candida albicans filaments and A549 human alveolar epithelial cells. In contrast to abiotic surfaces, the interaction with biotic surfaces is independent of the CsuA/BABCDE-mediated pili. The interaction of A. baumannii 19606 with fungal and epithelial cells also results in their apoptotic death, a response that depends on the direct contact of bacteria with these two types of eukaryotic cells. Furthermore, the bacterial adhesion phenotype correlates with the ability of bacteria to invade A549 epithelial cells. Interestingly, the killing activity of cell-free culture supernatants proved to be protease and temperature sensitive, suggesting that its cytotoxic activity is due to secreted proteins, some of which are different from OmpA.The genus Acinetobacter is a genetically diverse group of aerobic, gram-negative, nonfermenting bacteria (48, 49). Although acinetobacters are commonly described as being ubiquitous nonpathogenic bacteria, those strains belonging to the Acinetobacter baumannii-Acinetobacter calcoaceticus cluster are emerging as relevant opportunistic human pathogens due to their increases in virulence and multidrug resistance (13,32,34). Members of this genus play an important role in nosocomial infections and have attracted particular attention in severe cases associated with intensive care unit patients (4, 53). These infections manifest as serious diseases in compromised human hosts, particularly in cases of ventilator-acquired pneumonia, urinary tract infections, septicemia, and wound infections. More recently, A. baumannii has emerged as a serious pathogen among soldiers returning from Iraq and Afghanistan, with those suffering penetrating injuries being at the highest risk (9,12,13,32,34,57). These are some of the reports that demonstrate the emergence of A. baumannii as a relevant pathogen that causes severe infections in civilian and military medical facilities. These infections are extremely difficult to handle because of the multiple-antibiotic-resistance phenotype of most clinical isolates.The capacity of A. baumannii to cause disease in compromised patients and persist in the medical environment could be attributed to its resistance to major antimicrobial drugs (34) and desiccation (18), the latter of which is greater than that described for the Enterobacteriaceae and similar to that observed for Staphylococcus aureu...

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Section: Discussionmentioning

confidence: 88%

The Acinetobacter baumannii 19606 OmpA Protein Plays a Role in Biofilm Formation on Abiotic Surfaces and in the Interaction of This Pathogen with Eukaryotic Cells

2009

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“…An intriguing observation that ethanol stimulates the virulence of A. baumannii (39) led to the identification of a number of genes affecting virulence toward Caenorhabditis elegans and Dictyostelium discoideum (40) that await further characterization. A well-characterized porin of A. baumannii, the 38-kDa outer membrane protein A, has been shown to induce apoptosis of eukaryotic cells (9) and to activate dendritic cells, leading to the differentiation of CD4 ϩ T cells toward a Th1 phenotype (26). Finally, it was noted that A. baumannii forms biofilms with enhanced antibiotic resistance (48,49) and, more recently, that a chaperone-usher secretion system involved in pilus assembly affects biofilm formation (44).…”

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confidence: 99%

Identification and Characterization of an Acinetobacter baumannii Biofilm-Associated Protein

Luke²,

2008

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We have identified a homologue to the staphylococcal biofilm-associated protein (Bap) in a bloodstream isolate of Acinetobacter baumannii. The fully sequenced open reading frame is 25,863 bp and encodes a protein with a predicted molecular mass of 854 kDa. Analysis of the nucleotide sequence reveals a repetitive structure consistent with bacterial cell surface adhesins. Bap-specific monoclonal antibody (MAb) 6E3 was generated to an epitope conserved among 41% of A. baumannii strains isolated during a recent outbreak in the U.S. military health care system. Flow cytometry confirms that the MAb 6E3 epitope is surface exposed. Random transposon mutagenesis was used to generate A. baumannii bap1302::EZ-Tn5, a mutant negative for surface reactivity to MAb 6E3 in which the transposon disrupts the coding sequence of bap. Time course confocal laser scanning microscopy and three-dimensional image analysis of actively growing biofilms demonstrates that this mutant is unable to sustain biofilm thickness and volume, suggesting a role for Bap in supporting the development of the mature biofilm structure. This is the first identification of a specific cell surface protein directly involved in biofilm formation by A. baumannii and suggests that Bap is involved in intercellular adhesion within the mature biofilm.

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“…It has been reported that DCs bind to OmpA proteins from K. pneumoniae, E. coli, and A. baumannii, inducing DC maturation and activation, including expression of costimulatory molecules, cytokine secretion, and stimulation of T-cell proliferation (34,43,71). These observations, among others, have led to the designation of this highly conserved family of bacterial proteins as a new PAMP (33).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it was reported that recombinant OmpA proteins from Escherichia coli O157:H7, Klebsiella pneumoniae, and Acinetobacter baumannii interact with and induce maturation of DCs, an observation that resulted in the designation of the OmpA family of bacterial proteins as a new pathogen-associated molecular pattern (PAMP) (32,33,43,71). As OMP P5 is a member of the OmpA family of proteins (64), we also wanted to determine whether LB1, which is derived from OMP P5, showed properties similar to those of a PAMP (i.e., the ability to interact with and induce the maturation of DCs), among others.…”

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confidence: 99%

Differential Uptake and Processing of a Haemophilus influenzae P5-Derived Immunogen by Chinchilla Dendritic Cells

2008

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Dendritic cells (DCs) are potent antigen-presenting cells involved in the initiation and modulation of immune responses after immunization via their ability to process and present antigen to naive T cells. We wanted to examine the role of DCs in the development of protective immunity against nontypeable Haemophilus influenzae (NTHI)-induced experimental otitis media (OM) after intranasal immunization of chinchillas with an NTHI P5-derived synthetic peptide immunogen called LB1. As chinchilla DCs have not been described, we adapted well-established protocols to induce the differentiation of chinchilla bone marrow precursor cells into DCs, which resulted in cells that were morphologically and phenotypically similar to DCs of other species. In vitro, chinchilla DCs readily internalized LB1, upregulated expression of the maturation markers CD80 and major histocompatibility complex class II, and presented processed LB1 to primed CD3 ؉ T cells, which resulted in antigen-specific T-cell proliferation. In vivo, LB1-activated DCs trafficked from the chinchilla nasal cavity primarily to the nasal-associated lymphoid tissues and were detected in close proximity to CD3 ؉ T cells within this lymphoid aggregate. These data are the first to characterize chinchilla DCs and their functional properties. Furthermore, they suggest an important role for chinchilla DCs in the development of protective immunity against experimental NTHI-induced OM after intranasal immunization.

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Outer membrane protein A of Acinetobacter baumannii induces differentiation of CD4+ T cells toward a Th1 polarizing phenotype through the activation of dendritic cells

Cited by 63 publications

References 29 publications

The Acinetobacter baumannii 19606 OmpA Protein Plays a Role in Biofilm Formation on Abiotic Surfaces and in the Interaction of This Pathogen with Eukaryotic Cells

The Acinetobacter baumannii 19606 OmpA Protein Plays a Role in Biofilm Formation on Abiotic Surfaces and in the Interaction of This Pathogen with Eukaryotic Cells

Identification and Characterization of an Acinetobacter baumannii Biofilm-Associated Protein

Differential Uptake and Processing of a Haemophilus influenzae P5-Derived Immunogen by Chinchilla Dendritic Cells

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