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

Abstract

Rhinoscleroma is a human specific chronic disease characterized by the formation of granuloma in the airways, caused by the bacterium Klebsiella pneumoniae subspecies rhinoscleromatis, a species very closely related to K. pneumoniae subspecies pneumoniae. 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 upon K. rhinoscleromatis infection in a CCR2-independent manner. While K. pneumoniae and K. rhinoscleromatis infections induced a classical inflammatory reaction, K. rhinoscleromatis infection 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.

Respiratory scleroma: A clinicopathologic study of 51 cases from Guatemala

“…Partially digested bacteria seen in this stage might explain previously described bacilli presenting variable shapes (Gaafar, El‐Ghazzawi, Awaad, & Harada, ; Gaafar & Harada, ). However, as the infection progresses, KR are no longer digested and accumulate inside large vacuoles in MC, which is in agreement with studies using a RS murine model (Corelli et al, ; Fevre et al, ).…”

“…KR infection is characterized by an intense production of interleukin‐10 (IL‐10), an anti‐inflammatory cytokine necessary for the maturation of inflammatory monocytes in MC. These cells are also unable to destroy KR, which proliferates initially in small vacuoles and finally in a single large vacuole (Fevre et al, ), as illustrated in our microscopic and SEM findings. Furthermore, despite capsule polysaccharide is an important virulence factor in bacteria, type K3 capsule of KR may not play an important role in MC formation (Corelli et al, ).…”

“…Microscopically, Mikulicz cells (MC) are the hallmark of RS, which are atypical foamy macrophages unable to digest phagocytized K. rhinoscleromatis , persisting in highly enlarged vacuoles (Corelli et al, ). These cells appear after the non‐specific inflammatory reaction present in the atrophic stage, when bacteria are released into tissues after incomplete digestion and cell death (Fevre et al, ). In the fibrotic stage, the inflammatory infiltrate is replaced by extensive areas of fibrosis, when MC identification may become challenging (Fawaz, Tiba, Salman, & Othman, ).…”

Difficulties in diagnosing and treating nasal rhinoscleroma: A case study

“…13,19 This finding might be one of the positive markers for diagnostics of RS; however, additional levels of other inflammatory markers such as CRP (C-reactive protein) and procalcitonin levels might vary in the cases with or without a severe inflammation component. 11,13,14,20 It seems that a biopsy with microbiological scrubs are the most accurate factors for identifying RS. [2][3][4]19 A careful clinical examination should always be performed.…”

“…4,12 When present, in most cases it is found in the upper respiratory tract, mimicking tumorlike hard inflammatory infiltrations. [13][14][15][16] In some cases, its growth is misdiagnosed with cancer occurrence. 3,10,16 In available data a large number of inflammatory cells which corresponds with the degree of destruction of the nasal cartilage and nasal septum were found.…”