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

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Presentation on theme: "Fungal airway infection and proteinase-dependent atopy and asthma: an emerging paradigm."— Presentation transcript:

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

4 Caveats 1.The exogenous (environmental) causes of asthma remain obscure. 2.These findings were derived from an experimental model using ovalbumin, an allergen with no human disease relevance.

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

6 Integration of Innate and Adaptive Immune Signaling PathwaysProteolyticAllergen1 Th2 Cell (IL-13)4 Pro-AllergicChemokines CCL17, CCL7, 2 3 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 P.Porter, PhD Paul Porter, PhD Fungal Infection Versus Fungal Hypersensitivity?

9 Dust Sample #12 Fungal Culture From Sample #12 Dust Sample #24 Fungal Culture From Sample #24 85kDa 200kDa 7kDa Zymogram of House Dust Reveals Active Fungal Proteinases 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)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) Paul Porter, PhD 1.A common household fungus (A. niger) readily infects the mouse airway 2.Airway fungal infection both elicits and is required for allergic lung disease. Is this ABPA?

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 Paul Porter, PhD 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.

18 Putative Spectrum of Fungal- Dependent Allergic Lung Disease Antibody positiveAntibody negative 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 1.A. niger and other fungi cause allergic lung disease through airway infection and secretion of proteinases. 2.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: Baylor College of Medicine Farrah Kheradmand Stuart Abramson Sumanth Polikepahad Morgan Knight Paul Porter Yuping Qian Wendy Tai LaKeisha Batts Luz Roberts Alexander Seryshev Tianshu Yang Wen Lu Valentine Ongeri Manisha Singh Jeong-Soo Hong Anna Fields U. TX. Health Sciences Center George L. Delclos Joy De Los Reyes Supported by: NIH: HL075243, AI057696, AI070973, NIH: HL075243, AI057696, AI070973, HL095382


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