Role of Lung Epithelial Cells in Defense against Klebsiella pneumoniae

By Haya Harris

The airway epithelium represents a primary site for the entry of pathogenic bacteria into the lungs. It has been suggested for many respiratory pathogens, including Klebsiella pneumoniae, that invasion of the lung epithelial cells is an early stage of the pneumonia process.

Klebsiella pneumoniae is a pathogen that frequently causes hospital-acquired infections, mainly in immunocompromised patients. Klebsiella pneumoniae infections range from mild urinary infections to severe bacteremia and pneumonia with a high mortality and morbidity rate [1,2,3].

Commensal microflora, also called indigenous microbiota, is a complex set of bacteria and protozoa. It is located under the superficial layer of the skin and is on a large part of the mucosal surface, which is characterized by overlying mucosal fluids such as nasal and bronchial mucus. This bacterial microbiota is present from birth and maintains a commensal relationship, which is a natural biological interaction between two living beings. Recent studies show that the bacterial microbiota confers colonization resistance against bacterial pathogens. “It is already well known how commensal bacteria in the gut fight off pathogens,” explains co-first author Soner Yildiz, a postdoctoral research fellow at the Department of Microbiology and Molecular Medicine of UNIGE Faculty of Medicine, “but how lung bacteria carry out this role is less clear.”

Experimental evidence suggests that capsular polysaccharide (CPS) may be important for the establishment of pneumonia caused by K. pneumoniae, since active immunization with purified CPS protected rats against lethal experimentally-induced Klebsiella pneumonia [4].

Furthermore, in a more recent study, monoclonal antibodies, which are antibodies made by cloning a unique white blood cell, against Klebsiella CPS reduced the severity and hematogenous spread of K. pneumoniae [5]. Although these results are in agreement with the clinical observation that the encapsulated strains are usually highly virulent, they contradict recent studies by showing that unencapsulated strains invaded lung epithelial cells more efficiently than encapsulated strains [6].

Internalization of K. pneumoniae by human alveolar epithelial cells represents a mechanism to contain infection. Additionally, C3 produced by epithelial cells interacts with the bacteria and facilitates its elimination. CPS allows the bacteria to evade both mechanisms, leading to pneumonia and dissemination of the infection.

References

1. Bartlett, J. G., P. O'Keefe, F. P. Tally, T. J. Louie, and S. L. Gorbach. 1986. Bacteriology of hospital-acquired pneumonia. Arch. Intern. Med. 146:868-871. [PubMed] [Google Scholar]

2. Cryz, S. J., Jr., E. Fürer, and R. Germanier. 1986. Immunization against fatal experimental Klebsiella pneumoniae pneumonia. Infect. Immun. 54:403-407. [PMC free article] [PubMed] [Google Scholar]

3. Favre-Bonte, S., B. Joly, and C. Forestier. 1999. Consequences of reduction of Klebsiella pneumoniae capsule expression on interactions of this bacterium with epithelial cells. Infect. Immun.67:554-561. [PMC free article] [PubMed] [Google Scholar]

4. García de la Torre, M., J. Romero-Vivas, J. Martínez-Beltrán, A. Guerrero, M. Messeguer, and E. Bouza. 1985. Klebsiella bacteremia: an analysis of 100 episodes. Rev. Infect. Dis. 7:143-150. [PubMed] [Google Scholar]

5. Held, T. K., M. Trautmann, M. E. Mielke, H. Neudeck, S. J. Cryz, and A. Cross. 1992. Monoclonal antibody against Klebsiella capsular polysaccharide reduces severity and hematogenous spread of experimental Klebsiella pneumoniae pneumonia. Infect. Immun. 60:1771-1778. [PMC free article][PubMed] [Google Scholar]

6. Jarvis, W. R., V. P. Munn, A. K. Highsmith, D. H. Culver, and J. M. Hughes. 1985. The epidemiology of nosocomial infections caused by Klebsiella pneumoniae. Infect. Control 6:68-74. [PubMed] [Google Scholar]