This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fierer, J.
Right arrow Articles by Kirkland, T. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fierer, J.
Right arrow Articles by Kirkland, T. N.

 Previous Article  |  Next Article 

Infection and Immunity, September 1998, p. 4397-4402, Vol. 66, No. 9
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Importance of Interleukin-10 in Genetic Susceptibility of Mice to Coccidioides immitis

Joshua Fierer,1,2,* Lorraine Walls,3 Lars Eckmann,4 Tomoko Yamamoto,3,dagger and Theo N. Kirkland1,2

Medical and Pathology Services1 and Research Service,3 VA San Diego Healthcare System, and Departments of Medicine and Pathology2 and Department of Medicine,4 University of California, San Diego, San Diego, California

Received 17 April 1997/Returned for modification 26 May 1997/Accepted 21 June 1998

Inbred strains of mice vary in their susceptibility to Coccidioides immitis. We infected resistant DBA/2 (D2) mice and three susceptible strains of mice (C57BL/6 [B6], BALB/c, and CAST/Ei) by intraperitoneal injection of arthroconidia and determined the severity of infection based on colony counts of fungus in the spleens and lungs 14 days after infection. We used quantitative reverse transcription-PCR to measure the amounts of cytokines made in the spleens and lungs of infected mice. Susceptible mice made 1,000-fold more interleukin-10 (IL-10) than resistant D2 mice and about 10-fold more IL-4. In contrast, D2 mice had more IL-12 p40 in their lungs than did B6 mice. Resistant and susceptible mice made equivalent amounts of gamma interferon, IL-6, and IL-2. In order to determine whether IL-10 adversely affected the response to C. immitis, we infected IL-10-deficient mice, and they were found to be as resistant as D2 mice. This result indicates that IL-10 plays a crucial role in determining susceptibility to C. immitis in inbred mice. Because IL-4 mRNA levels were higher in most strains of susceptible mice, we also infected IL-4-deficient B6 mice. They were more resistant than B6 controls but not as resistant as IL-10-deficient mice. Thus, both IL-10 and IL-4 adversely affect the ability of C57BL mice to resist infection with C. immitis, but IL-10 has a larger effect and is the cytokine that is consistently associated with susceptibility in all strains of inbred mice.


* Corresponding author. Mailing address: Infectious Diseases Section (111F), VA San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA 92161. Phone: (619) 552-7446. Fax: (619) 552-4398. E-mail: jfierer{at}ucsd.edu.

dagger Present address: Chubu National Hospital, Obu City, Japan.


Infection and Immunity, September 1998, p. 4397-4402, Vol. 66, No. 9
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Shubitz, L. F., Dial, S. M., Perrill, R., Casement, R., Galgiani, J. N. (2008). Vaccine-Induced Cellular Immune Responses Differ from Innate Responses in Susceptible and Resistant Strains of Mice Infected with Coccidioides posadasii. Infect. Immun. 76: 5553-5564 [Abstract] [Full Text]  
  • Jimenez, M. d. P., Walls, L., Fierer, J. (2006). High Levels of Interleukin-10 Impair Resistance to Pulmonary Coccidioidomycosis in Mice in Part through Control of Nitric Oxide Synthase 2 Expression.. Infect. Immun. 74: 3387-3395 [Abstract] [Full Text]  
  • Li, L., Dial, S. M., Schmelz, M., Rennels, M. A., Ampel, N. M. (2005). Cellular Immune Suppressor Activity Resides in Lymphocyte Cell Clusters Adjacent to Granulomata in Human Coccidioidomycosis. Infect. Immun. 73: 3923-3928 [Abstract] [Full Text]  
  • He, Q., Moore, T. T., Eko, F. O., Lyn, D., Ananaba, G. A., Martin, A., Singh, S., James, L., Stiles, J., Black, C. M., Igietseme, J. U. (2005). Molecular Basis for the Potency of IL-10-Deficient Dendritic Cells as a Highly Efficient APC System for Activating Th1 Response. J. Immunol. 174: 4860-4869 [Abstract] [Full Text]  
  • Scheckelhoff, M., Deepe, G. S. Jr. (2005). A Deficiency in Gamma Interferon or Interleukin-10 Modulates T-Cell-Dependent Responses to Heat Shock Protein 60 from Histoplasma capsulatum. Infect. Immun. 73: 2129-2134 [Abstract] [Full Text]  
  • Cox, R. A., Magee, D. M. (2004). Coccidioidomycosis: Host Response and Vaccine Development. Clin. Microbiol. Rev. 17: 804-839 [Abstract] [Full Text]  
  • Deepe, G. S. Jr., Gibbons, R. S. (2003). Protective and Memory Immunity to Histoplasma capsulatum in the Absence of IL-10. J. Immunol. 171: 5353-5362 [Abstract] [Full Text]  
  • Li, K., Yu, J.-J., Hung, C.-Y., Lehmann, P. F., Cole, G. T. (2001). Recombinant Urease and Urease DNA of Coccidioides immitis Elicit an Immunoprotective Response against Coccidioidomycosis in Mice. Infect. Immun. 69: 2878-2887 [Abstract] [Full Text]  
  • Igietseme, J. U., Ananaba, G. A., Bolier, J., Bowers, S., Moore, T., Belay, T., Eko, F. O., Lyn, D., Black, C. M. (2000). Suppression of Endogenous IL-10 Gene Expression in Dendritic Cells Enhances Antigen Presentation for Specific Th1 Induction: Potential for Cellular Vaccine Development. J. Immunol. 164: 4212-4219 [Abstract] [Full Text]  
  • Fierer, J., Walls, L., Wright, F., Kirkland, T. N. (1999). Genes Influencing Resistance to Coccidioides immitis and the Interleukin-10 Response Map to Chromosomes 4 and 6 in Mice. Infect. Immun. 67: 2916-2919 [Abstract] [Full Text]