Molecular Pathology of Rickettsial Lung Infections

Rickettsial infections of humans comprise a diverse group of infections caused by pathogens that are obligate intracellular bacteria with a genetic relationship, including the genera Rickettsia, Orientia, Ehrlichia, and Anaplasma. The host cells of these pathogens largely belie the systemic clinical manifestations, because Rickettsia and Orientia infect endothelial cells, and Ehrlichia and Anaplasma infect circulating leukocytes (monocytes and neutrophils, respectively). Thus, the predominant manifestations (fever, headache, myalgia, with or without rash) do not usually focus attention on the respiratory system; however, the underlying pathogenesis of these infections involves degrees of vascular compromise either by direct injury and inflammation or by the action of vasoactive proinflammatory molecules such as cytokines, chemokines, and prostaglandins. Given that the lung possesses the largest vascular bed in the human body, it is not surprising that pulmonary involvement is periodically identified and, when severely affected, is considered a potentially life-threatening complication.1,2