Suppression of airway inflammation by a natural acute infection of the intestinal epithelium.
Although chronic intestinal helminth infections may suppress allergen-induced airway pathology by inducing a combination of modified T-helper (Th) 2 and immunosuppressive cytokines, a similar capacity of natural acute intestinal infections has remained untested, despite their global prevalence. Here, we show that allergic airway phenotypes including eosinophilia, eotaxin mRNA, and Th2 cytokines are significantly suppressed in animals that were infected by and that have cleared the intestinal parasite Eimeria vermiformis. Unlike in helminth-infected animals, regulation requires temporal coincidence of infection with sensitization; depends on interferon-gamma; and is not associated with an enhanced antigen-specific immunoglobulin G1 response. Moreover, regulation was effective following allergen sensitization in different anatomical sites, and in young and adult mice. These data highlight a transient anatomical dissemination of "functional immunologic dominance" following infection of the gut mucosa. They strongly support the hypothesis that airway allergies are naturally suppressed by both acute and chronic mucosal pathogens, but by different mechanisms.
Gibbons
D L
DL
Programme in Infection and Immunity, Peter Gorer Department of Immunobiology, King's College London, Guy's Hospital, London, UK.
Haque
S F Y
SF
Copestake
S L
SL
Wells
J W
JW
Noble
A
A
Smith
A L
AL
Hayday
A C
AC
D000375:Aging / Q000276:immunology*; D000818:Animals; D054413:Chemokine CCL11 / Q000276:immunology; D002908:Chronic Disease; D003048:Coccidiosis / Q000276:immunology* / Q000469:parasitology; D016207:Cytokines / Q000096:biosynthesis; D004539:Eimeria / Q000276:immunology / Q000378:metabolism*; D004802:Eosinophilia / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D033661:Oocysts / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D012137:Respiratory System / Q000276:immunology; D012140:Respiratory Tract Diseases / Q000139:chemically induced / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D054413:Chemokine CCL11; D016207:Cytokines; D007074:Immunoglobulin G; D007371:Interferon-gamma; D010047:Ovalbumin