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Infect. Immun. doi:10.1128/IAI.01712-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Murine innate immune response to virulent toxigenic and non-toxigenic Bacillus anthracis strains

Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, NM 87131; Department of Pathology, University of New Mexico Health Science Center, Albuquerque, NM 87131; Department of Microbiology and Molecular Genetics, The University of Texas Houston Health Science Center, Houston, Texas 77030; Department of Pathology, University of New Mexico Health Science Center, Albuquerque, NM 87131

^* To whom correspondence should be addressed. Email: Clyons{at}salud.unm.edu.

	Abstract

Effective treatment of anthrax is hampered by our limited understanding of the pathophysiology of Bacillus anthracis infection. We employed a genetically complete (pXO1+ pXO2+) virulent B. anthracis strain and four isogenic toxin null-mutants to determine the effects of the anthrax edema toxin (ET=edema factor (EF) + protective antigen (PA)) and lethal toxin (LT=lethal factor (LF) + PA) on host innate response during systemic infection. Using the spleen as an indicator for host response, we found that intravenous inoculation of LT-deficient mutants into C57BL/6 mice significantly increased production of several cytokines over that observed following infection with the parent strain or an EF-deficient mutant. Bacteria producing one or both of the toxins were capable of inducing significant apoptosis of cells present in spleens, whereas apoptosis was greatly reduced in mice infected with non-toxigenic mutants. Mice infected with toxin-producing strains also showed increased splenic neutrophil recruitment compared to mice infected with non-toxigenic strains and neutrophil depletion prior to infection with toxin-producing strains, lead to decreased levels of apoptosis. Together, these studies indicate that anthrax LT suppresses cytokine secretion during infection, but both EF and LF play roles in inducing neutrophil recruitment and enhancing apoptosis. Interestingly, in the absence of LF the effect of EF-induced cell recruitment is further enhanced, perhaps because LF so effectively suppresses the secretion of chemokines.