Infectious diseases affecting the lungs cause varying degrees of inflammation. Dysregulated inflammation is particularly deleterious and often associated with endothelial cell dysfunction. Trent et al. [31] reported dysregulated pulmonary inflammation and Tie-2-related endothelial dysfunction contributing to lung damage and mortality in a murine model of Orienta Tsutsugamushi infection. Tissue findings included a high level of Ang-2 proteins in pulmonary endothelial cells, a progressive loss of endothelial cell quiescent and junction proteins, and a substantial decrease in Tie-2 receptor at the transcriptional and functional levels. In-vitro infection of primary human endothelial cells demonstrated similar findings.