Monday 8 September 2008

Innate Immune System Targets Asthma-Linked Fungus For Destruction


A new study shows that the innate immune system of humans is capable of killing a fungus joined to flight path inflammation, chronic rhinosinusitis and bronchial bronchial asthma. Researchers at Mayo Clinic and the Virginia Bioinformatics Institute (VBI) have revealed that eosinophils, a picky type of white blood cell, exert a strong immune response against the environmental fungus Alternaria alternata. The groundbreaking findings, which shed light on some of the early events involved in the recognition of A. alternata by the human immune system, were published recently in the Journal of Immunology.*



Eosinophils typically armed combat parasitic invaders of the human dead body larger than bacteria or viruses, such as flukes or epenthetic worms (conjointly known as helminths). Evidence from different experimental approaches suggests that asthma and chronic sinusitis can arise when the body perceives that it has encountered a disease-causing organism. Environmental fungi such as Alternaria do not typically reason invasive infections like parasites but for some intellect, in certain people, the body responds as if it is being attacked and continuing inflammation can result from the ensuing cascade of immune-related events.



Principal Investigator Hirohito Kita, M.D., from Mayo Clinic, remarked: "Our results strongly show that eosinophils have the capacity to recognize and exert immunologic responses to certain fungi such as Alternaria. We have shown that CD11b receptors on the open of eosinophils recognize and adhere to beta-glucan, a major cell wall element of the fungus. This in turn sets in motion the release of toxic granule proteins by the white blood cells, leading to extensive price and ultimate destruction of the fungus. To the best of our noesis, this is the first time that live eosinophils and non just the intracellular components have been shown to target and destroy a fungus."



The researchers used fluorescence microscopy to determine the outcome of the interaction between eosinophils and A. alternata. The contact of fungus with eosinophils resulted in hopeful red fluorescence due to the damaged fungal cell wall and subsequent death of Alternaria. Immunohistochemistry confirmed the vent of toxic granular proteins by eosinophils due to contact with the fungus.



Dr. Chris Lawrence, Associate Professor at VBI and the Department of Biological Sciences at Virginia Tech, remarked: "T benefactor 2 (Th2) cells in the immune system typically produce cytokine signaling molecules or interleukins that tip to the recruitment of eosinophils for the dysregulated immune response commonly associated with air duct inflammatory disorders. Continual exposure of allergic individuals to common environmental fungi wish Alternaria may result in Th2 cells being forever activated to recruit eosinophils and this sustained defense team mechanism results in chronic inflammation. It has been shown previously that degranulation of eosinophils causes price of air duct mucosa and enhances firing. The next step in our transdisciplinary research collaboration will be to use recombinant fungous proteins and fungal kO mutants for specific genes to dissect the different molecular steps involved in the development and advancement of this acute immune response."



Hirohito Kita added: "We have taken an important step in showing that the congenital immune system of eosinophils is able of targeting an asthma-associated fungus for destruction. The biological significance of these results testament need to be verified further in animal models and in humans and our collaborative efforts with Dr. Lawrence's research grouping for proteomics and functional genomics will be priceless in this respect. We suspect that the dysregulated immune responses to Alternaria, other filamentlike fungi, and perhaps chitin-encased insects, such as mites and cockroaches, may toy a pivotal role in chronic lighting and the subsequent development of bronchial airway disease."


Notes:



* Juhan Yoon, Jens U. Ponikau, Christopher B. Lawrence, Hirohito Kita (2008)
Innate Antifungal Immunity of Human Eosinophils Mediated by a ?2 Integrin, CD11b. J. Immunol. 181: 2907-2915.



About VBI



The Virginia Bioinformatics Institute (VBI) at Virginia Tech (www.vbi.vt.edu) has a research platform centered on understanding the "disease triangle" of host-pathogen-environment interactions in plants, humans and other animals. By successfully channeling innovation into transdisciplinary approaches that combine information technology and biology, researchers at VBI are addressing some of today's key challenges in the biomedical, environmental and found sciences.



About Mayo Clinic



Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. Doctors from every medical specialty work together to care for patients, coupled by common systems and a ism of "the needs of the patient come first base." More than 3,three hundred physicians, scientists and researchers and 46,000 allied health staff work at Mayo Clinic, which has campuses in Rochester, Minn., Jacksonville, Fla., and Scottsdale/Phoenix, Ariz. Collectively, the deuce-ace locations treat more than half a million citizenry each year.



Source:

Barry Whyte
Virginia Tech



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