A Murine Inhalation Model to Characterize Pulmonary Exposure to Dry Aspergillus fumigatus Conidia

作者: Amanda D. Buskirk , Brett J. Green , Angela R. Lemons , Ajay P. Nayak , W. Travis Goldsmith

DOI: 10.1371/JOURNAL.PONE.0109855

关键词:

摘要: Most murine models of fungal exposure are based on the delivery uncharacterized extracts or liquid conidia suspensions using aspiration intranasal approaches. Studies that model to dry aerosols whole body inhalation have only recently been described. In this study, we aimed characterize pulmonary immune responses following repeated utilizing an acoustical generator deliver mice housed in a nose chamber. Immunocompetent female BALB/cJ were exposed derived from Aspergillus fumigatus wild-type (WT) melanin-deficient (Δalb1) strain. Conidia aerosolized and delivered at estimated deposition dose 1×105 twice week for 4 weeks (8 total). Histopathological immunological endpoints assessed 4, 24, 48, 72 hours after final exposure. analysis showed both strains induced lung inflammation, especially 24 48 hour time points. Immunological evaluated bronchoalveolar lavage fluid (BALF) mediastinal lymph nodes WT led elevated numbers macrophages, granulocytes, lymphocytes. Importantly, CD8+ IL17+ (Tc17) cells significantly higher BALF positively correlated with germination A. spores. Germination was associated specific IgG intracellular proteins while Δalb1 spores elicited antibodies cell wall hydrophobin. These data suggest exposures may provide more representative environmentally occupationally prevalent contaminants.

参考文章(41)
Elisabeth Heseltine, Jerome Rosen, None, WHO guidelines for indoor air quality : dampness and mould WHO. ,(2009)
Bart N. Lambrecht, Hamida Hammad, Taking our breath away: dendritic cells in the pathogenesis of asthma Nature Reviews Immunology. ,vol. 3, pp. 994- 1003 ,(2003) , 10.1038/NRI1249
B. J. Green, K. J. Cummings, W. R. Rittenour, J. M. Hettick, T. A. Bledsoe, F. M. Blachere, P. D. Siegel, D. M. Gaughan, G. J. Kullman, K. Kreiss, J. Cox-Ganser, D. H. Beezhold, Occupational sensitization to soy allergens in workers at a processing facility. Clinical & Experimental Allergy. ,vol. 41, pp. 1022- 1030 ,(2011) , 10.1111/J.1365-2222.2011.03756.X
Reto Crameri, Michael Weichel, Sabine Flückiger, Andreas G. Glaser, Claudio Rhyner, Fungal allergies: a yet unsolved problem. Chemical immunology and allergy. ,vol. 91, pp. 121- 133 ,(2006) , 10.1159/000090276
Maria de la Luz Garcia-Hernandez, Joyce B. Reome, Sara K. Misra, Tara M. Strutt, Kai K. McKinstry, Andrea M. Cooper, Susan L. Swain, Richard W. Dutton, Hiromasa Hamada, Tc17, a Unique Subset of CD8 T Cells That Can Protect against Lethal Influenza Challenge Journal of Immunology. ,vol. 182, pp. 3469- 3481 ,(2009) , 10.4049/JIMMUNOL.0801814
J. Lacey, R. Rylander, B. Fogelmark, Experimental allergic alveolitis after exposure to different microorganisms. International Journal of Experimental Pathology. ,vol. 72, pp. 387- 395 ,(1991)
Louis Y.A. Chai, Mihai G. Netea, Janyce Sugui, Alieke G. Vonk, Wendy W.J. van de Sande, Adilia Warris, Kyung J. Kwon-Chung, Bart Jan Kullberg, Aspergillus fumigatus Conidial Melanin Modulates Host Cytokine Response Immunobiology. ,vol. 215, pp. 915- 920 ,(2010) , 10.1016/J.IMBIO.2009.10.002
Birgit Simon-Nobbe, Ursula Denk, Verena Pöll, Raphaela Rid, Michael Breitenbach, The spectrum of fungal allergy. International Archives of Allergy and Immunology. ,vol. 145, pp. 58- 86 ,(2008) , 10.1159/000107578
Irma A.J.M. Bakker-Woudenberg, Experimental models of pulmonary infection. Journal of Microbiological Methods. ,vol. 54, pp. 295- 313 ,(2003) , 10.1016/S0167-7012(03)00118-0