Distinct CD4+-T-cell responses to live and heat-inactivated Aspergillus fumigatus conidia Journal Article

Authors: Rivera, A.; Van Epps, H. L.; Hohl, T. M.; Rizzuto, G.; Pamer, E. G.
Article Title: Distinct CD4+-T-cell responses to live and heat-inactivated Aspergillus fumigatus conidia
Abstract: 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 intra-tracheal challenge with live or heat-inactivated A. fumigatus spores. Live but not heat-inactivated fungal spores resulted in recruitment of gamma interferon (IFN-γ)-producing, fungus-specific CD4+ T cells to lung airways, achieving A. famigatus-specific frequencies exceeding 5% of total CD4+ T cells. While heat-inactivated spores did not induce detectable levels of IFN-γ-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. Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Keywords: nonhuman; lymph nodes; polymerase chain reaction; cell proliferation; t lymphocyte; mouse; animals; mice; immune system; gene expression; interleukin 13; interleukin 4; animal experiment; animal model; enzyme linked immunosorbent assay; mice, inbred c57bl; b-lymphocytes; molecular cloning; cytokine; th2 cell; lymphocyte activation; cellular immunity; gamma interferon; nucleotide sequence; lymph node; cd4-positive t-lymphocytes; western blotting; cytokine production; cd4 antigen; th1 cell; lung infection; aspergillus; aspergillus fumigatus; conidium; aspergillosis; fungus spore; lung aspergillosis; airway; complementary dna; polyacrylamide gel electrophoresis; spores, fungal; interferon type ii; polyclonal antibody; lung mycosis; heat; antibodies, fungal; antigens, fungal; lung alveolus
Journal Title: Infection and Immunity
Volume: 73
Issue: 11
ISSN: 0019-9567
Publisher: American Society for Microbiology  
Date Published: 2005-11-01
Start Page: 7170
End Page: 7179
Language: English
DOI: 10.1128/iai.73.11.7170-7179.2005
PUBMED: 16239511
PROVIDER: scopus
PMCID: PMC1273880
Notes: --- - "Cited By (since 1996): 35" - "Export Date: 24 October 2012" - "CODEN: INFIB" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Tobias Martin Hohl
    76 Hohl
  2. Eric Pamer
    277 Pamer
  3. Gabrielle A Rizzuto
    21 Rizzuto