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Media type:
E-Article
Title:
Distinct CD4+-T-Cell Responses to Live and Heat-InactivatedAspergillus fumigatusConidia
Contributor:
Rivera, Amariliz;
Van Epps, Heather L.;
Hohl, Tobias M.;
Rizzuto, Gabrielle;
Pamer, Eric G.
imprint:
American Society for Microbiology, 2005
Published in:Infection and Immunity
Language:
English
DOI:
10.1128/iai.73.11.7170-7179.2005
ISSN:
0019-9567;
1098-5522
Origination:
Footnote:
Description:
<jats:title>ABSTRACT</jats:title><jats:p><jats:italic>Aspergillus fumigatus</jats:italic>is an important fungal pathogen that causes invasive pulmonary disease in immunocompromised hosts. Respiratory exposure to<jats:italic>A. fumigatus</jats:italic>spores also causes allergic bronchopulmonary aspergillosis, a Th2 CD4<jats:sup>+</jats:sup>-T-cell-mediated disease that accompanies asthma. The microbial factors that influence the differentiation of<jats:italic>A. fumigatus</jats:italic>-specific CD4<jats:sup>+</jats:sup>T lymphocytes into Th1 versus Th2 cells remain incompletely defined. We therefore examined CD4<jats:sup>+</jats:sup>-T-cell responses of immunologically intact mice to intratracheal challenge with live or heat-inactivated<jats:italic>A. fumigatus</jats:italic>spores. Live but not heat-inactivated fungal spores resulted in recruitment of gamma interferon (IFN-γ)-producing, fungus-specific CD4<jats:sup>+</jats:sup>T cells to lung airways, achieving<jats:italic>A. fumigatus</jats:italic>-specific frequencies exceeding 5% of total CD4<jats:sup>+</jats:sup>T cells. While heat-inactivated spores did not induce detectable levels of IFN-γ-producing,<jats:italic>A. fumigatus</jats:italic>-specific CD4<jats:sup>+</jats:sup>T cells in the airways, they did prime CD4<jats:sup>+</jats:sup>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,<jats:italic>A. fumigatus</jats:italic>-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.</jats:p>