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Fungal airway infection and proteinase-dependent atopy and asthma: an emerging paradigm

Fungal airway infection and proteinase-dependent atopy and asthma: an emerging paradigm. Asthma is an Inflammatory Disease of the Airways. (Adapted from Greenlee, Werb, Kheradmand; Physiol Review 2007 Jan;87(1):69-98,

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Fungal airway infection and proteinase-dependent atopy and asthma: an emerging paradigm

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  1. Fungal airway infection and proteinase-dependent atopy and asthma: an emerging paradigm

  2. Asthma is an Inflammatory Disease of the Airways (Adapted from Greenlee, Werb, Kheradmand; Physiol Review 2007 Jan;87(1):69-98, nhlbi.nih.gov/health/dci/images/asthma.gif and apps.uwhealth.org/images/en/19321.jpg)

  3. What Can The Mouse Tell Us About Asthma? Eosinophil Corry, D.B.

  4. Caveats The exogenous (environmental) causes of asthma remain obscure. These findings were derived from an experimental model using ovalbumin, an allergen with no human disease relevance.

  5. Fungi Pollen Intestinal worms Proteinases and Asthma Natural Sources of Proteases Linked to Asthma

  6. 1 Proteolytic Allergen Th2 Cell (IL-13) 4 3 Pro-Allergic Chemokines CCL17, CCL7, 2 Integration of Innate and Adaptive Immune Signaling Pathways Kiss A, et. al.,. J Allergy Clin Immunol 2007; 120:334-342

  7. Can we learn more about the environmental causes of asthma by sifting through house dust? How Do Microbial Proteinases Relate to Asthma?

  8. Typical Fungal Crop From a Houston House Dust Sample Fungal Infection Versus Fungal Hypersensitivity? Paul Porter, PhD P.Porter, PhD

  9. Zymogram of House Dust Reveals Active Fungal Proteinases 85kDa 200kDa 7kDa Fungal Culture From Sample #24 Fungal Culture From Sample #12 Dust Sample #24 Dust Sample #12 P Porter, et al. Mucosal Immunol. 2009; 2:504-517

  10. Aspergillus niger Reservoirs: found ubiquitously in soil world wild and common in homes. Human infections (rare): Invasive sinobronchial aspergillosis, otomycosis Many industrial uses: food industry 80-85% of secreted protease is aspergillopepsin I (43kDa) P.Porter, PhD

  11. Viable Fungal Spores (A. niger) Are Required for Allergic Lung Disease P Porter, et al. Mucosal Immunol. 2009; 2:504-517

  12. Universal Potential for AHR Induced by Household Fungi P. Porter et al., submitted

  13. Mouse BAL Fluid Hyphae (A. niger) A common household fungus (A. niger) readily infects the mouse airway Airway fungal infection both elicits and is required for allergic lung disease. Is this ABPA? Paul Porter, PhD

  14. Conidia-Dependent Allergic Lung Disease Is Dose Dependent P Porter, et al. Mucosal Immunol. 2009; 2:504-517

  15. Low-Grade A. niger Infection Induces Atopy to Innocuous Antigens and Synergistic ALD P Porter, et al. Mucosal Immunol. 2009; 2:504-517

  16. Ovalbumin-Specific Th2 Responses Generated in Spleen by Fungal Infection P Porter, et al. Mucosal Immunol. 2009; 2:504-517

  17. Summary 1. A ubiquitous household fungus (A. niger) accounts for much of the detectable household proteinase activity in Houston. 2. A. niger infection induces allergic lung disease in mice through active infection. 3. A. niger induces atopy to bystander antigens, but not itself. Paul Porter, PhD

  18. Putative Spectrum of Fungal-Dependent Allergic Lung Disease Antibody negative Antibody positive Fungal Infectious Burden Disease Severity

  19. IL-13 is Required for Fungal Clearance P Porter, et al. Mucosal Immunol. 2009; 2:504-517

  20. Mouse Eosinophils Are Fungicidal A. fumigatus P Porter, et al. Mucosal Immunol. 2009; 2:504-517

  21. Conclusions A. niger and other fungi cause allergic lung disease through airway infection and secretion of proteinases. Common household fungi are candidate infectious causes of human respiratory tract allergic diseases and atopy. Future Studies Apply advanced methods of detection and immunodiagnosis to determine the etiological role of fungi in all forms of asthma.

  22. Many Thanks To:

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