Klebsiella rhinoscleromatis, the etiological agent of rhinoscleroma.

February 13, 2017

Rhinoscleroma, a neglected disease

Rhinoscleroma is a human specific chronic, progressive, granulomatous infection disease that affects the upper airways and is frequently associated with the nose (Figure 1). This disease has affected human beings for more than a thousand years and, although considered a rare disease, it is endemic in poor populations of Middle East, Eastern Europe, tropical Africa, South and Central America and South East Asia. Acquisition of the disease is facilitated by poor hygienic conditions, malnutrition and young adults, 10 to 30 years of age, are frequently affected. Rhinoscleroma is difficult to treat since the relapse rate is often high. Current therapies involve prolonged antibiotic therapy and/or surgery.

Figure 1. Photogravure of rhinoscleroma (source of the image: Wikipedia).

Klebsiella pneumoniae subsp. rhinoscleromatis

Rhinoscleroma is caused by the bacterium Klebsiella pneumoniae susbspecies rhinoscleromatis (KR), a species very closely related to K. pneumoniae subspecies pneumoniae (KP). It is a Gram – negative capsulated bacterium that is strictly associated with humans. Even if it is genetically very close related to KP, these two bacteria cause very different disease. While KP is responsible for acute pneumonia infection, KR can persist in the human host causing the chronic disease known as rhinoscleroma. Why these two bacteria so genetically close cause so different disease remains to be deciphered.

Very little is known about the pathophysiology of rhinoscleroma. Our laboratory hypothesized that Mikulicz cells play a central role in creating the environment that sets the stage for chronic inflammation.

Mikulicz cells, the hallmark of rhinoscleroma

Rhinoscleroma is characterized by the appearance of specific foamy phagocytic cells containing ingested bacteria called Mikulicz cells.

Our laboratory developed a murine model of rhinoscleroma, recapitulating the formation of Mikulicz cells in lungs and found that Mikulicz cells are atypical inflammatory monocytes specifically recruited from the bone marrow upon KR infection. Moreover, KR infection is characterized by the intense production of an anti-inflammatory cytokine, interleukin-10, that is essential for the maturation of the inflammatory monocytes into Mikulicz cells. These findings from our laboratory have been published as the first cellular and molecular characterization of rhinoscleroma and of the environment leading to Mikulicz cells maturation.

Check the publication and the hard work of my colleagues:

C. Fevre et al., A novel murine model of rhinoscleroma identifies Mikulicz cells, the disease signature, as IL-10 dependent derivatives of inflammatory monocytes, EMBO Mol Med 5, 516–530 (2013).

From my side, as a parallel work of my main PhD research project, I want to explore the effect of the bacterial capsule on the pathogenesis of Klebsiella rhinoscleromatis. We aim to use a capsule defective strain of Klebsiella rhinoscleromatis, constructed in the laboratory, to study the general involvement of the capsule in Klebsiella rhinoscleromatis-host interaction and in the particular in the maturation of Mikulicz cells.

This project is in progress…INBIONET folks, stay tuned!