Mycobacterial trehalose dimycolate reprograms macrophage global gene expression and activates matrix metalloproteinases.

Trehalose 6,6′-dimycolate (TDM) is a cell wall glycolipid and an important virulence factor of mycobacteria. In order to study the role of TDM in the innate immune response to Mycobacterium tuberculosis, microarray analysis was used to examine gene regulation in murine bone marrow-derived macrophages in response to 90-μm-diameter polystyrene microspheres coated with TDM. A large number of genes, particularly those involved in the immune response and macrophage function, were up- or downregulated in response to these TDM-coated beads compared to control beads. Genes involved in the immune response were specifically upregulated in a myeloid differentiation primary response gene 88 (MyD88)-dependent manner. The complexity of the transcriptional response also increased greatly between 2 and 24 h. Matrix metalloproteinases (MMPs) were significantly upregulated at both time points, and this was confirmed by quantitative real-time reverse transcription-PCR (RT-PCR). Using an in vivo Matrigel granuloma model, the presence and activity of MMP-9 were examined by immunohistochemistry and in situ zymography (ISZ), respectively. We found that TDM-coated beads induced MMP-9 expression and activity in Matrigel granulomas. Macrophages were primarily responsible for MMP-9 expression, as granulomas from neutrophil-depleted mice showed staining patterns similar to that for wild-type mice. The relevance of these observations to human disease is supported by the similar induction of MMP-9 in human caseous tuberculosis (TB) granulomas. Given that MMPs likely play an important role in both the construction and breakdown of tuberculous granulomas, our results suggest that TDM may drive MMP expression during TB pathogenesis

New Rodenticides: An Update on Recent Research Trials

Rodents cause substantial amounts of damage and losses of foodstuffs around the world. While various methods are used to reduce damage and losses to rodents, rodenticides remain the most important tool in the toolbox. However, like all tools, rodenticides have advantages and disadvantages. Several considerations are shaping the future of rodenticide use. These include manufacturing and registration costs, concern about toxicity levels and non-target animal hazards, potential hazards to children, reduced effectiveness of some formulations, and humaneness to the targeted rodents. While there have been very few new developments in rodenticides in the last several decades, new formulations and active ingredients need to be investigated so that these concerns can be addressed. We are conducting studies on some new materials: sodium nitrite, lower concentrations of zinc phosphide, and two-active ingredient formulations (cholecalciferol plus diphacinone). Preliminary results are promising with a number of rodent species. Some materials (sodium nitrite and zinc phosphide) have been encapsulated to avoid low palatability and bait shyness issues. Preliminary cage study results are presented as well as proposed future studies