Protective efficacy of IgA monoclonal antibodies to O and H antigens in a mouse model of intranasal challenge with Salmonella enterica serotype Enteritidis

Iankov, Ianko; Petrov, Danail; Mladenov, I; Haralambieva, Iana H.; Kalev, Ognian; Balabanova, Maria S.; Mitov, Ivan

doi:10.1016/j.micinf.2004.05.007

Cited by 35 publications

(29 citation statements)

References 53 publications

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“…In the intestinal lumen, the most measurable response to infection is the appearance of secretory IgA (SIgA) antibodies directed against S. Typhimurium surface antigens, notably flagella and the O antigen (O-Ag). While the exact contribution of antiflagellar antibodies to intestinal immunity remains unresolved, it is well established that SIgA antibodies against O-Ag are protective (22,33,39,40). This was first demonstrated experimentally by Michetti and colleagues, who showed that transport of Sal4, a polymeric IgA monoclonal antibody (MAb) against the Salmonella O5 antigen, into the intestinal tracts of mice was sufficient to protect the animals against an otherwise lethal oral dose of virulent S. Typhimurium (39).…”

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confidence: 99%

Association of a Protective Monoclonal IgA with the O Antigen of Salmonella enterica Serovar Typhimurium Impacts Type 3 Secretion and Outer Membrane Integrity

et al. 2012

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ABSTRACTInvasion of intestinal epithelial cells bySalmonella entericaserovar Typhimurium is an energetically demanding process, involving the transfer of effector proteins from invading bacteria into host cells via a specialized organelle known as theSalmonellapathogenicity island 1 (SPI-1) type 3 secretion system (T3SS). By a mechanism that remains poorly understood, entry ofS. Typhimurium into epithelial cells is inhibited by Sal4, a monoclonal, polymeric IgA antibody that binds an immunodominant epitope within the O-antigen (O-Ag) component of lipopolysaccharide. In this study, we investigated how the binding of Sal4 to the surface ofS. Typhimurium influences T3SS activity, bacterial energetics, and outer membrane integrity. We found that Sal4 treatment impaired T3SS-mediated translocon formation and attenuated the delivery of tagged effector proteins into epithelial cells. Sal4 treatment coincided with a partial reduction in membrane energetics and intracellular ATP levels, possibly explaining the impairment in T3SS activity. Sal4's effects on bacterial secretion and energetics occurred concurrently with an increase in O-Ag levels in culture supernatants, alterations in outer membrane permeability, and changes in surface ultrastructure, as revealed by transmission electron microscopy and cryo-electron microscopy. We propose that Sal4, by virtue of its ability to bind and cross-link the O-Ag, induces a form of outer membrane stress that compromises the integrity of theS. Typhimurium cell envelope and temporarily renders the bacterium avirulent.

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Association of a Protective Monoclonal IgA with the O Antigen of Salmonella enterica Serovar Typhimurium Impacts Type 3 Secretion and Outer Membrane Integrity

et al. 2012

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“…In the intestinal tract, secretory immunoglobulin A (SIgA) antibodies directed against the O antigen of serovar Typhimurium are sufficient to prevent mucosal infection (11,26,36,47). This was first demonstrated experimentally by Kraehenbuhl and Neutra and Michetti and colleagues who produced and characterized a collection of B-cell hybridomas isolated from the Peyer's patches of mice immunized with an attenuated strain of serovar Typhimurium (32,36).…”

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Inhibition of Salmonella enterica Serovar Typhimurium Motility and Entry into Epithelial Cells by a Protective Antilipopolysaccharide Monoclonal Immunoglobulin A Antibody

2008

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Secretory immunoglobulin A (SIgA) antibodies directed against the O antigen of lipopolysaccharide (LPS)are the primary determinants of mucosal immunity to gram-negative enteric pathogens. However, the underlying mechanisms by which these antibodies interfere with bacterial colonization and invasion of intestinal epithelial cells are not well understood. In this study, we report that Sal4, a protective, anti-O5-specific monoclonal IgA, is a potent inhibitor of Salmonella enterica serovar Typhimurium flagellum-based motility. Using video light microscopy, we observed that Sal4 completely and virtually instantaneously "paralyzed" laboratory and clinical strains of serovar Typhimurium. Sal4-mediated motility arrest preceded and occurred independently of agglutination. Polyclonal anti-LPS IgG antibodies and F(ab) 2 fragments were as potent as was Sal4 at impeding bacterial motility, whereas monovalent Fab fragments were 5-to 10-fold less effective. To determine whether motility arrest can fully account for Sal4's protective capacity in vitro, we performed epithelial cell infection assays in which the requirement for flagellar motility in adherence and invasion was bypassed by centrifugation. Under these conditions, Sal4-treated serovar Typhimurium cells remained noninvasive, revealing that the monoclonal IgA, in addition to interfering with motility, has an effect on bacterial uptake into epithelial cells. Sal4 did not, however, inhibit bacterial uptake into mouse macrophages, indicating that the antibody interferes specifically with Salmonella pathogenicity island 1 (SPI-1)-dependent, but not SPI-1-independent, entry into host cells. These results reveal a previously unrecognized capacity of SIgA to "disarm" microbial pathogens on mucosal surfaces and prevent colonization and invasion of the intestinal epithelium.

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“…These antibodies also effectively reduced the nasal carriage of influenza virus in a mouse model (34). However, there are conflicting reports regarding the contribution of IgA to immunity against gram-negative bacterial pathogens (1,17,18,22).…”

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confidence: 99%

Comparative Role of Immunoglobulin A in Protective Immunity against the Bordetellae

Wolfe¹,

Kirimanjeswara²,

Goebel

et al. 2007

Infect Immun

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The genus Bordetella includes a group of closely related mammalian pathogens that cause a variety of respiratory diseases in a long list of animals (B. bronchiseptica) and whooping cough in humans (B. pertussis and B. parapertussis). While past research has examined how these pathogens are eliminated from the lower respiratory tract, the host factors that control and/or clear the bordetellae from the upper respiratory tract remain unclear. We hypothesized that immunoglobulin A (IgA), the predominant mucosal antibody isotype, would have a protective role against these mucosal pathogens. IgA ؊/؊ mice were indistinguishable from wild-type mice in their control and clearance of B. pertussis or B. parapertussis, suggesting that IgA is not crucial to immunity to these organisms. However, naïve and convalescent IgA ؊/؊ mice were defective in reducing the numbers of B. bronchiseptica in the upper respiratory tract compared to wild-type controls. Passively transferred serum from convalescent IgA ؊/؊ mice was not as effective as serum from convalescent wild-type mice in clearing this pathogen from the tracheae of naive recipient mice. IgA induced by B. bronchiseptica infection predominantly recognized lipopolysaccharide-containing O-antigen, and antibodies against O-antigen were important to bacterial clearance from the trachea. Since an IgA response contributes to the control of B.

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Protective efficacy of IgA monoclonal antibodies to O and H antigens in a mouse model of intranasal challenge with Salmonella enterica serotype Enteritidis

Cited by 35 publications

References 53 publications

Association of a Protective Monoclonal IgA with the O Antigen of Salmonella enterica Serovar Typhimurium Impacts Type 3 Secretion and Outer Membrane Integrity

Association of a Protective Monoclonal IgA with the O Antigen of Salmonella enterica Serovar Typhimurium Impacts Type 3 Secretion and Outer Membrane Integrity

Inhibition of Salmonella enterica Serovar Typhimurium Motility and Entry into Epithelial Cells by a Protective Antilipopolysaccharide Monoclonal Immunoglobulin A Antibody

Comparative Role of Immunoglobulin A in Protective Immunity against the Bordetellae

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