Noncapsulated<i>Klebsiella pneumoniae</i>Bearing Mannose-Containing O Antigens Is Rapidly Eradicated from Mouse Lung and Triggers Cytokine Production by Macrophages following Opsonization with Surfactant Protein D

Kostina, E.O; Ofek, Itzhak; Crouch, Erika C.; Friedman, Rotem; Sirota, Lea; Klinger, G; Sahly, Hany; Keisari, Yona

doi:10.1128/iai.73.12.8282-8290.2005

Cited by 26 publications

(29 citation statements)

References 48 publications

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“…Klebsiella serotypes that express a CPS with di-Man/Rha glycoepitopes were significantly less virulent than serotypes that do not. Moreover, the lung clearance of di-Man/Rha-bearing Klebsiella strains was significantly enhanced compared to that of Klebsiella strains lacking such glycoepitopes in their CPS (41). Thus, the chemical structure of the capsule partially determines the virulence of K. pneumoniae in mice, consistent with the roles of the MR and SP-A and possibly of DC-SIGN too.…”

Section: Capsular Glycoepitope-dependent Clearance Of Klebsiella In Msupporting

confidence: 58%

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Recognition of Bacterial Surface Polysaccharides by Lectins of the Innate Immune System and Its Contribution to Defense against Infection: the Case of Pulmonary Pathogens

et al. 2008

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5Many pathogenic bacterial species are classified into serological types, distinguished by their carbohydrate-rich surface antigens. These antigens are referred to as serotypic epitopes or glycoepitopes. Glycoepitopes are most commonly associated with capsular polysaccharides (CPS) or the O-antigen domains of bacterial lipopolysaccharides (LPS).The association of specific bacterial serotypes of a given genus with defined clinical infections is a common phenomenon that applies to a variety of gram-negative bacteria and gram-positive bacteria. As discussed below, of the 77 distinct capsular serotypes in the species Klebsiella pneumoniae, only 25 account for most pulmonary and blood infections (12). Likewise, of the more than 90 capsular serotypes of Streptococcus pneumoniae, only 23 account for most infections, and these are included in the current capsular vaccine (25).The surfaces of the pulmonary pathogens Klebsiella pneumoniae and Streptococcus pneumoniae are coated with a variety of glycoconjugates that confer specific properties. For example, the polysaccharide capsules enable these pathogens to resist phagocytosis. In a few cases, it has been argued that serotype-associated differences in capsular size contribute to virulence and the high frequency of isolation. However, there is no satisfactory explanation why only a limited number of capsular serotypes are responsible for most infections (12,25).Because lectins are important components of the lung's innate immune system, it is reasonable to hypothesize that differences in the frequencies of isolation of specific serotypes in the setting of pneumonia are in part determined by the recognition, or the lack of recognition, of their corresponding glycoepitopes by lectins. We propose that the lack of recognition of glycoconjugates by one or more lectins of the lung contributes to the high frequency of isolation from pneumonia patients of the pulmonary pathogens bearing reactive glycoepitopes. Conversely, lectins that recognize serotype-specific glycoepitopes contribute to the eradication of these serotypes, resulting in a lower frequency of their isolation from clinical samples.In this review, we first correlate the sugar specificities of several types of lung lectins with the glycoconjugates on the surfaces of selected pulmonary pathogens. We then briefly describe in vitro data that suggest mechanisms through which the lung C-type lectins contribute to the elimination of specific glycoepitope-bearing serotypes. Finally, we review available evidence supporting our hypothesis that the high frequency of isolation of serotypes bearing a specific glycoepitope results from the ability of these serotypes to evade recognition by lectins of the innate immune system. PULMONARY LECTINS OF THE INNATE IMMUNE SYSTEMDuring the last 3 decades, there has been intensive research on animal lectins (59, 90). Although lung lectins play a variety of homeostatic roles (38, 89), considerable research has focused on the contributions of several lectins to the innate, natural defense s...

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Section: Capsular Glycoepitope-dependent Clearance Of Klebsiella In Msupporting

confidence: 58%

“…In contrast, O1 serotypes showed a lower cytokine response and were inefficiently cleared in vivo. This did not occur in macrophagedepleted mice (41).…”

Section: Interaction Of Klebsiella O Antigen Of Lps With C-type Lectinsmentioning

confidence: 87%

Recognition of Bacterial Surface Polysaccharides by Lectins of the Innate Immune System and Its Contribution to Defense against Infection: the Case of Pulmonary Pathogens

et al. 2008

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“…In mouse infection models, no significant differences were found in K. pneumoniae bacterial loads in the lungs between complement-depleted and control mice during lung infection (142). In contrast, there is much more strain-to-strain variability in the susceptibility of K. pneumoniae to antimicrobial peptides and proteins, such as defensins and surfactants, depending upon the specific antimicrobial (143,(149)(150)(151)(152). For example, human beta defensin 1 (HBD-1) and HBD-2 are not as efficient at killing K. pneumoniae as HBD-3 (149).…”

Section: K Pneumoniae and Host Immune Defensesmentioning

confidence: 88%

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

Paczosa

Mecsas

2016

Microbiol Mol Biol Rev

1,364

1,345

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SUMMARYKlebsiella pneumoniaecauses a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically,K. pneumoniaehas caused serious infection primarily in immunocompromised individuals, but the recent emergence and spread of hypervirulent strains have broadened the number of people susceptible to infections to include those who are healthy and immunosufficient. Furthermore,K. pneumoniaestrains have become increasingly resistant to antibiotics, rendering infection by these strains very challenging to treat. The emergence of hypervirulent and antibiotic-resistant strains has driven a number of recent studies. Work has described the worldwide spread of one drug-resistant strain and a host defense axis, interleukin-17 (IL-17), that is important for controlling infection. Four factors, capsule, lipopolysaccharide, fimbriae, and siderophores, have been well studied and are important for virulence in at least one infection model. Several other factors have been less well characterized but are also important in at least one infection model. However, there is a significant amount of heterogeneity inK. pneumoniaestrains, and not every factor plays the same critical role in all virulentKlebsiellastrains. Recent studies have identified additionalK. pneumoniaevirulence factors and led to more insights about factors important for the growth of this pathogen at a variety of tissue sites. Many of these genes encode proteins that function in metabolism and the regulation of transcription. However, much work is left to be done in characterizing these newly discovered factors, understanding how infections differ between healthy and immunocompromised patients, and identifying attractive bacterial or host targets for treating these infections.

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“…Several studies have described the role of K. pneumoniae surface polysaccharides in interactions with macrophages or human epithelial cells, in which CPS seemed to impede cell association and cellular activation whereas LPS seemed to increase cell association, but little is known about interactions with human DCs (8,12,13,16,24,34,35,39).…”

Section: Discussionmentioning

confidence: 99%

Roles of Capsule and Lipopolysaccharide O Antigen in Interactions of Human Monocyte-Derived Dendritic Cells and Klebsiella pneumoniae

Evrard¹,

Balestrino

Dosgilbert

et al. 2010

Infect Immun

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In humans, Klebsiella pneumoniae is a saprophytic bacterium of the nasopharyngeal and intestinal mucosae that is also frequently responsible for severe nosocomial infections. Two major factors of virulence, capsular polysaccharide (CPS) and lipopolysaccharide (LPS) O antigen, are involved in mucosal colonization and the development of infections. These bacterial surface structures are likely to play major roles in interactions with the mucosal immune system, which are orchestrated by a network of surveillance based on dendritic cells (DCs). To determine the roles of K. pneumoniae CPS and LPS in the DC response, we investigated the response of immature human monocyte-derived DCs to bacterial challenge with a wild-type strain and its isogenic mutants deficient in CPS or LPS O-antigen production. As observed by flow cytometry and confocal laser microscopy, the rate of phagocytosis was inversely proportional to the amount of CPS on the bacterial cell surface, with LPS playing little or no role. The K. pneumoniae wild-type strain induced DC maturation with upregulation of CD83, CD86, and TLR4 and downregulation of CD14 and DC-SIGN. With CPS mutants, we observed a greater decrease in DC-SIGN, suggesting a superior maturation of DCs. In addition, incubation of DCs with CPS mutants, and to a lesser extent with LPS mutants, resulted in significantly higher Th1 cytokine production. Combined, our findings suggest that K. pneumoniae CPS, by hampering bacterial binding and internalization, induces a defective immunological host response, including maturation of DCs and pro-Th1 cytokine production, whereas the LPS O antigen seems to be involved essentially in DC activation.

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NoncapsulatedKlebsiella pneumoniaeBearing Mannose-Containing O Antigens Is Rapidly Eradicated from Mouse Lung and Triggers Cytokine Production by Macrophages following Opsonization with Surfactant Protein D

Cited by 26 publications

References 48 publications

Recognition of Bacterial Surface Polysaccharides by Lectins of the Innate Immune System and Its Contribution to Defense against Infection: the Case of Pulmonary Pathogens

Recognition of Bacterial Surface Polysaccharides by Lectins of the Innate Immune System and Its Contribution to Defense against Infection: the Case of Pulmonary Pathogens

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

Roles of Capsule and Lipopolysaccharide O Antigen in Interactions of Human Monocyte-Derived Dendritic Cells and Klebsiella pneumoniae

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