Innate immune system targets asthma-linked fungus for destruction

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Public release date: 2-Sep-2008

Innate immune system targets asthma-linked fungus for destruction

EurekAlert (press release) - Washington,DC*

Contact: Barry Whyte

whyte@...

540-231-1767

Virginia Tech

http://www.eurekalert.org/pub_releases/2008-09/vt-iis090208.php

Blacksburg, Va. – A new study shows that the innate immune system of

humans is capable of killing a fungus linked to airway inflammation,

chronic rhinosinusitis and bronchial asthma. Researchers at Mayo

Clinic and the Virginia Bioinformatics Institute (VBI) have revealed

that eosinophils, a particular 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 combat parasitic invaders of the human body

larger than bacteria or viruses, such as flukes or parasitic worms

(collectively 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 cause invasive infections like parasites but for some

reason, in certain people, the body responds as if it is being

attacked and chronic inflammation can result from the ensuing

cascade of immune-related events.

Principal Investigator Hirohito Kita, M.D., from Mayo Clinic,

remarked: " Our results strongly demonstrate that eosinophils have

the capacity to recognize and exert immunological responses to

certain fungi such as Alternaria. We have shown that CD11b receptors

on the surface of eosinophils recognize and adhere to beta-glucan, a

major cell wall component of the fungus. This in turn sets in motion

the release of toxic granule proteins by the white blood cells,

leading to extensive damage and ultimate destruction of the fungus.

To the best of our knowledge, this is the first time that live

eosinophils and not 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 bright red

fluorescence due to the damaged fungal cell wall and subsequent

death of Alternaria. Immunohistochemistry confirmed the release of

toxic granular proteins by eosinophils due to contact with the

fungus.

Dr. Lawrence, Associate Professor at VBI and the Department of

Biological Sciences at Virginia Tech, remarked: " T helper 2 (Th2)

cells in the immune system typically produce cytokine signaling

molecules or interleukins that lead to the recruitment of

eosinophils for the dysregulated immune response commonly associated

with airway inflammatory disorders. Continual exposure of sensitized

individuals to common environmental fungi like Alternaria may result

in Th2 cells being constantly activated to recruit eosinophils and

this sustained defense mechanism results in chronic inflammation. It

has been shown previously that degranulation of eosinophils causes

damage of airway mucosa and enhances inflammation. The next step in

our transdisciplinary research collaboration will be to use

recombinant fungal proteins and fungal knockout mutants for specific

genes to dissect the different molecular steps involved in the

development and progression of this acute immune response. "

Hirohito Kita added: " We have taken an important step in showing

that the innate immune system of eosinophils is capable of targeting

an asthma-associated fungus for destruction. The biological

significance of these results will need to be verified further in

animal models and in humans and our collaborative efforts with Dr.

Lawrence's research group for proteomics and functional genomics

will be invaluable in this respect. We suspect that the dysregulated

immune responses to Alternaria, other filamentous fungi, and perhaps

chitin-encased insects, such as mites and cockroaches, may play a

pivotal role in chronic inflammation and the subsequent development

of bronchial airway disease. "

###

* Juhan Yoon, Jens U. Ponikau, B. Lawrence, Hirohito

Kita (2008)

Innate Antifungal Immunity of Human Eosinophils Mediated by a â2

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 plant 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, joined by common systems and a

philosophy of " the needs of the patient come first. " More than 3,300

physicians, scientists and researchers and 46,000 allied health

staff work at Mayo Clinic, which has campuses in Rochester, Minn.,

ville, Fla., and sdale/Phoenix, Ariz. Collectively, the

three locations treat more than half a million people each year