Surfactant protein-A inhibits Aspergillus fumigatus-induced allergic T-cell responses

Seth Thomas Scanlon, Tatyana Milovanova, Sonja Kierstein, Yang Cao, Elena Nikolaevna Atochina, Yaniv Tomer, Scott J. Russo, Michael F. Beers, Angela Haczku

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14 Citations (Scopus)

Abstract

Background: The pulmonary surfactant protein (SP)-A has potent immunomodulatory activities but its role and regulation during allergic airway inflammation is unknown. Methods: We studied changes in SP-A expression in the bronchoalveolar lavage (BAL) using a murine model of single Aspergillus fumigatus (Af) challenge of sensitized animals. Results: SP-A protein levels in the BAL fluid showed a rapid, transient decline that reached the lowest values (25% of controls) 12 h after intranasal Af provocation of sensitized mice. Decrease of SP-A was associated with influx of inflammatory cells and increase of IL-4 and IL-5 mRNA and protein levels. Since levels of SP-A showed a significant negative correlation with these BAL cytokines (but not with IFN-γ), we hypothesized that SP-A exerts an inhibitory effect on Th2-type immune responses. To study this hypothesis, we used an in vitro Af-rechallenge model. Af-induced lymphocyte proliferation of cells isolated from sensitized mice was inhibited in a dose-dependent manner by addition of purified human SP-A (0.1-10 μg/ml). Flow cytometric studies on Af-stimulated lymphocytes indicated that the numbers of CD4+ (but not CD8+) T cells were significantly increased in the parental population and decreased in the third and fourth generation in the presence of SP-A. Further, addition of SP-A to the tissue culture inhibited Af-induced IL-4 and IL-5 production suggesting that SP-A directly suppressed allergen-stimulated CD4+ T cell function. Conclusion: We speculate that a transient lack of this lung collectin following allergen exposure of the airways may significantly contribute to the development of a T-cell dependent allergic immune response.

Original languageEnglish
Article number97
JournalRespiratory Research
Volume6
DOIs
Publication statusPublished - 24 Aug 2005
Externally publishedYes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Medicine(all)

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    Scanlon, S. T., Milovanova, T., Kierstein, S., Cao, Y., Atochina, E. N., Tomer, Y., Russo, S. J., Beers, M. F., & Haczku, A. (2005). Surfactant protein-A inhibits Aspergillus fumigatus-induced allergic T-cell responses. Respiratory Research, 6, [97]. https://doi.org/10.1186/1465-9921-6-97