scholarly journals A Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Homologue Plays a Pivotal Role in Nontypeable Haemophilus influenzae Colonization of the Chinchilla Nasopharynx via the Outer Membrane Protein P5-Homologous Adhesin

2007 ◽  
Vol 76 (1) ◽  
pp. 48-55 ◽  
Author(s):  
James E. Bookwalter ◽  
Joseph A. Jurcisek ◽  
Scott D. Gray-Owen ◽  
Soledad Fernandez ◽  
Glen McGillivary ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Haemophilus Influenzae ◽  
Carcinoembryonic Antigen ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Bacterial Pathogen ◽  
Nontypeable Haemophilus Influenzae ◽  
Bacterial Adhesins

ABSTRACT In vitro studies suggest an important role for CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) in infection by multiple gram-negative bacteria. However, in vivo evidence supporting this role is lacking, largely because the bacterial adhesins involved in this host-microbe association do not bind to murine-derived CEACAM1. One of several adhesins expressed by nontypeable Haemophilus influenzae (NTHI), the outer membrane protein P5-homologous adhesin (or P5), is essential for colonization of the chinchilla nasopharynx and infection of the middle ear. Here we reveal that NTHI P5 binds to the chinchilla homologue of CEACAM1 and that rabbit anti-human carcinoembryonic antigen blocks NTHI colonization of the chinchilla nasopharynx, providing the first demonstration of a role for CEACAM receptor binding by any bacterial pathogen in vivo.

scholarly journals Outer Membrane Protein P6 of Nontypeable Haemophilus influenzae Is a Potent and Selective Inducer of Human Macrophage Proinflammatory Cytokines

2005 ◽  
Vol 73 (5) ◽  
pp. 2728-2735 ◽  
Author(s):  
Charles S. Berenson ◽  
Timothy F. Murphy ◽  
Catherine T. Wrona ◽  
Sanjay Sethi
Keyword(s):  
Membrane Protein ◽  
Haemophilus Influenzae ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Human Macrophage ◽  
Nontypeable Haemophilus Influenzae ◽  
Human Macrophages ◽  
Tnf Α ◽  
Factor Α

ABSTRACT Interactions of nontypeable Haemophilus influenzae (NTHI) with human macrophages contribute to the pathogenesis of NTHI-induced infection in humans. However, the immunologic mechanisms that initiate and perpetuate NTHI-mediated macrophage responses have not been well explored. Outer membrane protein (OMP) P6 is a conserved lipoprotein expressed by NTHI in vivo that possesses a Pam3Cys terminal motif, characteristic of immunoactive bacterial lipoproteins associated with Toll-like receptor signaling. We theorized that OMP P6 is a potent immunomodulator of human macrophages. To test this hypothesis, we purified OMP P6 as well as OMP P2, the predominant NTHI outer membrane protein, and lipooligosaccharide (LOS), the specific endotoxin of NTHI, from NTHI strain 1479. Human blood monocyte-derived macrophages, purified from healthy donors, were incubated with each outer membrane constituent, and cytokine production of macrophage supernatants interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), IL-10, IL-12, and IL-8 was measured. OMP P6 selectively upregulated IL-10, TNF-α, and IL-8. While OMP P6 (0.1 μg/ml for 8 h) elicited slightly greater concentrations of IL-10, it resulted in over ninefold greater concentrations of TNF-α and over fourfold greater concentrations of IL-8 than did OMP P2. OMP P6 at doses as low as 10 pg/ml was still effective at induction of macrophage IL-8, while OMP P2 and LOS were not. OMP P6 of NTHI is a specific trigger of bacteria-induced human macrophage inflammatory events, with IL-8 and TNF-α as key effectors of P6-induced macrophage responses.

scholarly journals Characterization of Specific Immune Responses of Mice Inoculated with Recombinant Vaccinia Virus Expressing an 18-Kilodalton Outer Membrane Protein of Brucella abortus

2000 ◽  
Vol 7 (1) ◽  
pp. 114-118 ◽  
Author(s):  
Ramesh Vemulapalli ◽  
Silvio Cravero ◽  
Christine L. Calvert ◽  
Thomas E. Toth ◽  
Nammalwar Sriranganathan ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Vaccinia Virus ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Brucella Abortus ◽  
Virulent Strain ◽  
Shuttle Vector ◽  
Protein Fusion

ABSTRACT Using the shuttle vector pMCO2 and the vaccinia virus wild-type WR strain, we constructed a recombinant virus expressing an 18-kDa outer membrane protein of Brucella abortus. BALB/c mice inoculated with this virus produced 18-kDa protein-specific antibodies, mostly of immunoglobulin G2a isotype, and in vitro stimulation of splenocytes from these mice with purified maltose binding protein–18-kDa protein fusion resulted in lymphocyte proliferation and gamma interferon production. However, these mice were not protected against a challenge with the virulent strain B. abortus2308. Disruption of the 18-kDa protein's gene in vaccine strainB. abortus RB51 did not affect either the strain's protective capabilities or its in vivo attenuation characteristics. These observations suggest that the 18-kDa protein plays no role in protective immunity.

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