Mice lacking tissue factor in myeloid cells are susceptible to Mycobacterium tuberculosis infection (P1243)

Abstract

Abstract Tissue Factor (TF) is a trans membrane glycoprotein important for initiation of the coagulation cascade. Recent observations indicate that TF is expressed in cancer, metabolic diseases and infections. In the current study, we determined the role of TF in M. tuberculosis (M. tb) infection using mice lacking the TF gene in myeloid cells (Cre+). One month after infection with the M. tb virulent laboratory strain, H37Rv, the lung bacterial burden was higher in Cre+ than Cre- mice (3.7 ± 0.2 X 106 vs 1.9 ± 0.1 X 106 CFU, p=0.01). M.tb infected Cre+ mice had more CD4+ and CD8+ lymphocytes and expressed 33 and 38 fold less of IFN-γ and IL-17 mRNA in the lungs, compared to Cre- mice, as measured by real time PCR. In contrast, lung IL-10 mRNA levels were higher in M. tb-infected Cre+ mice than Cre- mice (16.04 ± 3.3 vs 4.4 ± 1 fold, p=0.03). Immunohistochemical analysis indicated that M. tb-infected Cre+ mice had more foamy macrophages in the lungs than Cre- mice. M. tbH37Rv grew more rapidly in peritoneal exudate macrophages of Cre+ mice, compared to Cre- macrophages (6.1 ± 1 X 106 vs 1.5 ± 0.6 X 106 CFU, p=0.02). Further studies indicated that M. tb-infected Cre+ macrophages undergo less mitochondrial apoptosis than Cre- macrophages (16.2 ± 2.1vs 27.9 ± 1.4 %, p=0.01). Studies are underway to determine the mechanism/s involved in increased IL-10 production, reduced mitochondrial apoptosis and increased bacterial burden of M tb infected Cre+ mice.