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Infection and Immunity, December 2008, p. 5553-5564, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00885-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Vaccine-Induced Cellular Immune Responses Differ from Innate Responses in Susceptible and Resistant Strains of Mice Infected with Coccidioides posadasii{triangledown} ,{dagger}

Lisa F. Shubitz,1,3 Sharon M. Dial,1,2 Robert Perrill,3 Rachael Casement,2 and John N. Galgiani3,4*

Department of Veterinary Science and Microbiology,1 Arizona Veterinary Diagnostic Laboratory,2 Valley Fever Center for Excellence, The University of Arizona, Tucson, Arizona,3 Southern Arizona Veterans' Administration Health Care System, Tucson, Arizona4

Received 17 July 2008/ Returned for modification 28 July 2008/ Accepted 30 September 2008

Susceptibility to Coccidioides spp. varies widely in humans and other mammals and also among individuals within a species. Among strains of mice with various susceptibilities, immunohistopathology revealed that C57BL/6 mice were highly susceptible to the disease following intranasal infection, DBA/2n mice were intermediate, and Swiss-Webster mice were innately resistant. Resistant Swiss-Webster mice developed prominent perivascular/peribronchiolar lymphocytic cuffing and well-formed granulomas with few fungal elements and debris in the necrotic center, surrounded by a mantle of macrophages, lymphocytes, and fibrocytes. Susceptible C57BL/6 mice became moribund between 14 and 18 days postinfection, with overwhelming numbers of neutrophils and spherules and very few T cells, the drastic reduction of which was associated with failure and death, while intermediate DBA/2n mice controlled the fungal burden but demonstrated progressive lung inflammation with prominent suppuration, and they deteriorated clinically. Vaccinated C57BL/6 mice had an early and robust lymphocyte response, which included significantly higher Mac2+, CD3+, and CD4+ cell scores on day 18 than those of innately resistant SW mice and DBA/2n mice; they also had prominent perivascular/peribronchiolar lymphocytic infiltrates not present in their unvaccinated counterparts, and they appeared to be resolving lesions by day 56 compared to the other two strains, based on significantly lower disease scores and observably smaller and fewer lesions with few spherules and neutrophils.

* Corresponding author. Mailing address: Valley Fever Center for Excellence, P.O. Box 245215, The University of Arizona, Tucson, AZ 85724. Phone: (520) 626-4968. Fax: (520) 626-4971. E-mail: spherule{at}u.arizona.edu

{triangledown} Published ahead of print on 13 October 2008.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. Casadevall

Infection and Immunity, December 2008, p. 5553-5564, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00885-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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