A novel murine model of rhinoscleroma identifies Mikulicz cells, the disease signature, as IL-10 dependent derivatives of inflammatory monocytes

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Abstract

Rhinoscleroma is a human specific chronic disease characterized by the formation of granuloma in the airways, caused by the bacteriumKlebsiella pneumoniaesubspeciesrhinoscleromatis, a species very closely related toK. pneumoniaesubspeciespneumoniae. It is characterized by the appearance of specific foamy macrophages called Mikulicz cells. However, very little is known about the pathophysiological processes underlying rhinoscleroma. Herein, we characterized a murine model recapitulating the formation of Mikulicz cells in lungs and identified them as atypical inflammatory monocytes specifically recruited from the bone marrow uponK. rhinoscleromatisinfection in a CCR2-independent manner. WhileK. pneumoniaeandK. rhinoscleromatisinfections induced a classical inflammatory reaction,K. rhinoscleromatisinfection was characterized by a strong production of IL-10 concomitant to the appearance of Mikulicz cells. Strikingly, in the absence of IL-10, very few Mikulicz cells were observed, confirming a crucial role of IL-10 in the establishment of a proper environment leading to the maturation of these atypical monocytes. This is the first characterization of the environment leading to Mikulicz cells maturation and their identification as inflammatory monocytes.

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