Hot off the AJP Press!
Natural Killer Cells Promote Tissue Injury and Systemic Inflammatory Responses During Fatal Ehrlichia-Induced Toxic Shock-Like Syndrome
Stevenson HL, Estes MD, Thirumalapura NR, Walker DH, Ismail N.
Department of Pathology, University of Texas Medical Branch, the Sealy Center for Vaccine Development, and the Center for Biodefense and Emerging Infectious Diseases, Galveston, Texas; and the Departments of Pathology, Microbiology and Immunology, Meharry Medical College, Nashville, Tennessee Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Am J Pathol. 2010 Aug;177(2):766-776, DOI: 10.2353/ ajpath.2010.091110
A synopsis written by co-author and ASIP trainee Dr. Heather Stevenson, at the University of Texas Medical Branch in Galveston, TX
It is a very exciting time in the field of ehrlichiosis, with many recent discoveries providing answers to previously controversial or unknown questions. Ehrlichia are obligately intracellular bacteria that lack genes for lipopolysaccharide (LPS) and peptidoglycan, and reside within the early endosomes of monocytic cells inhibiting phagolysosome fusion. These bacteria are transmitted by ticks; the primary vector is Amblyomma americanum. The clinical presentation of human monocytotropic ehrlichiosis (HME) may be nonspecific, and the disease is difficult to diagnose. The intracellular microcolonies of bacteria that are prototypical of the disease are rarely identified in blood smears, a characteristic clinical sign, such as a rash, is observed in relatively few patients, and history of a tick bite may be lacking.
The clinical presentation of the disease is variable. Interstitial pneumonia, hepatic dysfunction, aseptic meningitis, and hemorrhages have been described. The severity of the disease is greater in elderly and immunocompromised patients; however, even in immunocompetent patients HME can be fatal. Even with susceptibility of Ehrlichia chaffeensis to doxycycline, the case fatality rate is still approximately 3%. Overwhelming ehrlichial infections occur mainly in immunocompromised patients, and in contrast fatal ehrlichiosis in immunocompetent patients occurs with a low bacterial load. In addition, hepatocytes have been observed to undergo apoptosis without evidence of ehrlichial infection. These characteristics, along with the clinical presentation resembling toxic shock-like syndrome, support the hypothesis that dysregulation of the host immune response leads to tissue damage and eventually multi-system organ failure.
One of the primary goals of our laboratories is to gain a better understanding of how this immune-mediated pathology is induced. Cell mediated immunity, orchestrated mainly by CD4+ Th1 cells, is required for protection against severe disease. Mouse models of HME also allow the determination of the factors that lead to the development of severe ehrlichiosis, which include high concentrations of TNF-