Affiliation:
1. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine
2. Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan
Abstract
ABSTRACT
Over the past four decades, there has been a significant increase in allergy and asthma in westernized countries, which correlates with alterations in fecal microbiota (microflora) and widespread use of antibiotics (the “hygiene hypothesis”). Antibiotics also lead to overgrowth of the yeast
Candida albicans
, which can secrete potent prostaglandin-like immune response modulators. We have developed a mouse model of antibiotic-induced microbiota disruption that includes stable increases in gastrointestinal (GI) enteric bacteria and GI
Candida
levels with no introduction of microbes into the lungs. Mice are treated for 5 days with cefoperazone in the drinking water, followed by a single oral gavage of
C. albicans
. This results in alterations of GI bacterial populations and increased yeast numbers in the GI microbiota for at least 2 to 3 weeks and can drive the development of a CD4 T-cell-mediated allergic airway response to subsequent mold spore (
Aspergillus fumigatus
) exposure in immunocompetent mice without previous systemic antigen priming. The allergic response in the lungs is characterized by increased levels of eosinophils, mast cells, interleukin-5 (IL-5), IL-13, gamma interferon, immunoglobulin E, and mucus-secreting cells. In the absence of antibiotics, mice exposed to
Aspergillus
spores do not develop an allergic response in the airways. This study provides the first experimental evidence to support a role for antibiotics and fungal microbiota in promoting the development of allergic airway disease. In addition, these studies also highlight the concept that events in distal mucosal sites such as the GI tract can play an important role in regulating immune responses in the lungs.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
255 articles.
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