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Infection and Immunity, August 2006, p. 4856-4864, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.00246-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

An Intradermal Environment Promotes a Protective Type-1 Response against Lethal Systemic Monocytotropic Ehrlichial Infection

Heather L. Stevenson, Jeffrey M. Jordan, Ziad Peerwani,{dagger} Hui-Qun Wang, David H. Walker, and Nahed Ismail*

Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

Received 14 February 2006/ Returned for modification 28 March 2006/ Accepted 30 May 2006

Immune responses against monocytotropic ehrlichiosis during infection with a strain of Ehrlichia from Ixodes ovatus (IOE) were evaluated using a model that closely reproduces the pathology and immunity associated with tick-transmitted human monocytotropic ehrlichiosis. C57BL/6 mice were inoculated intradermally or intraperitoneally with high-dose highly virulent IOE or intraperitoneally with mildly virulent Ehrlichia muris. Intradermal (i.d.) infection with IOE established mild, self-limited disease associated with minimal hepatic apoptosis, and all mice survived past 30 days. Intraperitoneal (i.p.) infection with IOE resulted in acute, severe toxic shock-like syndrome and severe multifocal hepatic apoptosis and necrosis, and all mice succumbed to disease. Compared to i.p. infection with IOE, intradermally infected mice had a 100- to 1,000-fold lower bacterial load in the spleen with limited dissemination. Compared to mice infected intraperitoneally with IOE, i.d. infection stimulated a stronger protective type-1 cell-mediated response on day 7 of infection, characterized by increased percentages of both CD4+ and CD8+ splenic T cells, generation of a greater number of IOE-specific, gamma interferon-producing CD4+ Th1 cells, and higher levels of tumor necrosis factor (TNF-{alpha}) in the spleen but lower concentrations of serum TNF-{alpha} and interleukin-10. These data suggest that under the conditions of natural route of challenge (i.e., i.d. inoculation), the immune response has the capacity to confer complete protection against monocytotropic ehrlichiosis, which is associated with a strong cell-mediated type-1 response and decreased systemic production of pro- and anti-inflammatory cytokines.

* Corresponding author. Mailing address: Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0609. Phone: (409) 772-3111. Fax: (409) 772-2500. E-mail: naismail{at}utmb.edu.

Editor: W. A. Petri, Jr.

{dagger} Present address: Division of Pathology and Clinical Laboratory Medicine, Cleveland Clinic Foundation, Cleveland, Ohio.

Infection and Immunity, August 2006, p. 4856-4864, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.00246-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Thirumalapura, N. R., Stevenson, H. L., Walker, D. H., Ismail, N. (2008). Protective Heterologous Immunity against Fatal Ehrlichiosis and Lack of Protection following Homologous Challenge. Infect. Immun. 76: 1920-1930 [Abstract] [Full Text]  
  • Stevenson, H. L., Crossley, E. C., Thirumalapura, N., Walker, D. H., Ismail, N. (2008). Regulatory Roles of CD1d-Restricted NKT Cells in the Induction of Toxic Shock-Like Syndrome in an Animal Model of Fatal Ehrlichiosis. Infect. Immun. 76: 1434-1444 [Abstract] [Full Text]  


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