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 Rivera, A.
Right arrow Articles by Pamer, E. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rivera, A.
Right arrow Articles by Pamer, E. G.

 Previous Article  |  Next Article 

Infection and Immunity, November 2005, p. 7170-7179, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7170-7179.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Distinct CD4+-T-Cell Responses to Live and Heat-Inactivated Aspergillus fumigatus Conidia

Amariliz Rivera,1 Heather L. Van Epps,1 Tobias M. Hohl,1 Gabrielle Rizzuto,2 and Eric G. Pamer1*

Infectious Diseases Service, Immunology Program, Department of Medicine, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center,1 Tri-Institutional MD/PhD Program, Sloan-Kettering Institute, New York, New York 100212

Received 26 May 2005/ Returned for modification 5 July 2005/ Accepted 8 August 2005

Aspergillus fumigatus is an important fungal pathogen that causes invasive pulmonary disease in immunocompromised hosts. Respiratory exposure to A. fumigatus spores also causes allergic bronchopulmonary aspergillosis, a Th2 CD4+-T-cell-mediated disease that accompanies asthma. The microbial factors that influence the differentiation of A. fumigatus-specific CD4+ T lymphocytes into Th1 versus Th2 cells remain incompletely defined. We therefore examined CD4+-T-cell responses of immunologically intact mice to intratracheal challenge with live or heat-inactivated A. fumigatus spores. Live but not heat-inactivated fungal spores resulted in recruitment of gamma interferon (IFN-{gamma})-producing, fungus-specific CD4+ T cells to lung airways, achieving A. fumigatus-specific frequencies exceeding 5% of total CD4+ T cells. While heat-inactivated spores did not induce detectable levels of IFN-{gamma}-producing, A. fumigatus-specific CD4+ T cells in the airways, they did prime CD4+ T-cell responses in draining lymph nodes that produced greater amounts of interleukin 4 (IL-4) and IL-13 than T cells responding to live conidia. While immunization with live fungal spores induced antibody responses, we found a marked decrease in isotype-switched, A. fumigatus-specific antibodies in sera of mice following immunization with heat-inactivated spores. Our studies demonstrate that robust Th1 T-cell and humoral responses are restricted to challenge with fungal spores that have the potential to germinate and cause invasive infection. How the adaptive immune system distinguishes between metabolically active and inactive fungal spores remains an important question.

* Corresponding author. Mailing address: Memorial Sloan-Kettering Cancer Center, Infectious Diseases Service, 1275 York Avenue, Box 9, New York, NY 10021. Phone: (212) 639-7809. Fax: (212) 717-3021. E-mail: pamere{at}mskcc.org.

Editor: T. R. Kozel

Infection and Immunity, November 2005, p. 7170-7179, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7170-7179.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Park, S. J., Mehrad, B. (2009). Innate Immunity to Aspergillus Species. Clin. Microbiol. Rev. 22: 535-551 [Abstract] [Full Text]  
  • Rivera, A., Collins, N., Stephan, M. T., Lipuma, L., Leiner, I., Pamer, E. G. (2009). Aberrant Tissue Localization of Fungus-Specific CD4+ T Cells in IL-10-Deficient Mice. J. Immunol. 183: 631-641 [Abstract] [Full Text]  
  • Park, S. J., Hughes, M. A., Burdick, M., Strieter, R. M., Mehrad, B. (2009). Early NK Cell-Derived IFN-{gamma} Is Essential to Host Defense in Neutropenic Invasive Aspergillosis. J. Immunol. 182: 4306-4312 [Abstract] [Full Text]  
  • Hohl, T. M., Feldmesser, M. (2007). Aspergillus fumigatus: Principles of Pathogenesis and Host Defense. Eukaryot Cell 6: 1953-1963 [Full Text]  
  • Gersuk, G. M., Underhill, D. M., Zhu, L., Marr, K. A. (2006). Dectin-1 and TLRs Permit Macrophages to Distinguish between Different Aspergillus fumigatus Cellular States. J. Immunol. 176: 3717-3724 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»