The role of neutrophils during Orientia infection.

Abstract

Abstract Scrub typhus is a seriously neglected disease with approximately one-third of the world’s population at risk of being infected with Orientia tsutsugamushi, and the occurrence of over one million scrub typhus cases annually illustrate its importance in global health. All scrub typhus case studies that report blood cell counts, describe neutrophilia during the course of infection. Patients with confirmed scrub typhus have significant increases in activated neutrophil proteins in serum, and the increase of neutrophil recruiting cytokines. We also observed neutrophilia as well as neutrophil recruitment to infected tissues in intravenously infected mice, suggesting key role for neutrophils in scrub typhus disease progression. To determine the role of neutrophils in this infection, female C57BL/6 mice were lethally challenged, and neutrophils were depleted one day prior to infection (D−1) or six (D+6) days post infection. The effects of neutrophil depletion were observed to be dependent on the time post infection. Animals depleted early (D-1) exhibited more severe pathology at an earlier time point and had disease progression similar to non-depleted animals but had greater survival. Animals depleted 6 dpi recovered weight, and signs of illness had resolved by 12 dpi. Histopathology demonstrated decreased cellular infiltrates when compared to infected, non-depleted animals. Depletion of neutrophils decreased mortality independent of when depleted, but only depletion 6 dpi resulted in amelioration of signs. These data suggest an important role of neutrophils in tissue pathology and disease progression during scrub typhus infection.