Innate antifungal immunity of human eosinophils mediated by a beta 2 integrin, CD11b.
Eosinophils produce and release various proinflammatory mediators and also show immunomodulatory and tissue remodeling functions; thus, eosinophils may be involved in the pathophysiology of asthma and other eosinophilic disorders as well as host defense. Several major questions still remain. For example, how do human eosinophils become activated in diseased tissues or at the site of an immune response? What types of host immunity might potentially involve eosinophils? Herein, we found that human eosinophils react vigorously to a common environmental fungus, Alternaria alternata, which is implicated in the development and/or exacerbation of human asthma. Eosinophils release their cytotoxic granule proteins, such as eosinophil-derived neurotoxin and major basic protein, into the extracellular milieu and onto the surface of fungal organisms and kill the fungus in a contact-dependent manner. Eosinophils use their versatile beta(2) integrin molecule, CD11b, to adhere to a major cell wall component, beta-glucan, but eosinophils do not express other common fungal receptors, such as dectin-1 and lactosylceramide. The I-domain of CD11b is distinctively involved in the eosinophils' interaction with beta-glucan. Eosinophils do not react with another fungal cell wall component, chitin. Because human eosinophils respond to and kill certain fungal organisms, our findings identify a previously unrecognized innate immune function for eosinophils. This immune response by eosinophils may benefit the host, but, in turn, it may also play a role in the development and/or exacerbation of eosinophil-related allergic human diseases, such as asthma.
Yoon
Juhan
J
Department of Immunology, Division of Allergic Disease, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, USA.
Ponikau
Jens U
JU
Lawrence
Christopher B
CB
Kita
Hirohito
H
D000528:Alternaria / Q000254:growth & development / Q000276:immunology*; D039481:CD11b Antigen / Q000378:metabolism / Q000502:physiology*; D018821:CD18 Antigens / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D015550:Cell Degranulation / Q000276:immunology; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D047071:beta-Glucans / Q000378:metabolism* / Q000494:pharmacology
D039481:CD11b Antigen; D018821:CD18 Antigens; D047071:beta-Glucans