An in vitro dual model of mycobacterial granulomas to investigate the molecular interactions between mycobacteria and human host cells.

In the majority of individuals infected with Mycobacterium tuberculosis, the bacilli cause a long-term asymptomatic infection called latent tuberculosis, a state during which the bacilli reside within granulomas. Latently infected individuals have around 10% risk of progression to clinical disease at a later stage. Determining the state of the mycobacteria and the host cells during this latent phase, i.e. within the granulomas, would greatly improve our understanding of the physiopathology of tuberculosis, and thus enable the development of new therapeutic means to treat the one-third of the world's population who are latently infected. We have developed an in vitro model of human mycobacterial granulomas, enabling the cellular and molecular analysis of the very first steps in the host granulomatous response to either mycobacterial compounds or live mycobacterial species. In vitro mycobacterial granulomas mimic natural granulomas very well, with the progressive recruitment of macrophages around live bacilli or mycobacterial antigen-coated beads, their differentiation into multinucleated giant cells and epithelioid cells, and the final recruitment of a ring of activated lymphocytes. Besides morphological similarities, in vitro granulomas also functionally resemble natural ones, with the development of intense cellular co-operation and intracellular mycobactericidal activities.

Histiocytic sarcoma in C57BL/6J female mice is associated with liver hematopoiesis: review of 41 cases.

Forty-one cases of histiocytic sarcoma (HS) in C57BL/6J mice were histopathologically studied with special regard to unexpected associated hematopoietic disorders. These cases were retrieved among C57BL/6J female mice used as control mice in a chronic low-dose irradiation experiment. Hematopoietic characteristics were analysed by comparison to 41 disease-free mice from the same cohort. Tumoral involvement of the liver was observed in all 41 HS-bearing mice, followed by infiltration of the spleen (61.8%), lung (32.4%), bone marrow (14.3%), uterus (12.2%), lymph node (9.8%), and kidney (2.4%). By comparative analysis, we were able to demonstrate a significant association of HS with liver hematopoiesis (89.5% in HS group vs 15% in control mice, p < 0.00001), and with central hematopoietic disorders involving the myelocytic cells (decreased in HS, p = 0.003) and erythrocytic cells (increased in HS, p = 0.001). Microscopic characteristics of these 41 cases and physiopathology of the newly described hematopoietic features in HS are further discussed.