Ascaris suum-derived products suppress mucosal allergic inflammation in an interleukin-10-independent manner via interference with dendritic cell function.
We have previously demonstrated that protection from allergic inflammation by Ascaris suum infection was characterized by a global increase in interleukin-10 (IL-10) and the development of protective CD4(+)/CD25(+) T cells (L. Schopf, S. Luccioli, V. Bundoc, P. Justice, C. C. Chan, B. J. Wetzel, H. H. Norris, J. F. Urban, Jr., and A. Keane-Myers, Investig. Ophthalmol. Vis. Sci. 46:2772-2780, 2005). Here, we used A. suum pseudocoelomic fluid (PCF) in lieu of infection to define molecular mechanisms of allergic protection in a mouse model of allergic inflammation. Mice were sensitized with ragweed (RW) and PCF (RW/PCF), PCF alone, or RW alone and then challenged intratracheally, intranasally, and supraocularly with RW. Histological examination of the eyes and lungs, analysis of the bronchoalveolar lavage fluid (BALF), and characterization of ex vivo cytokine responses were performed to determine allergic inflammatory responses. RW/PCF-treated mice had suppressed allergic immune responses compared to mice given RW alone. To investigate whether IL-10 was involved in PCF-mediated allergic protection, similar experiments were performed using mice genetically deficient for IL-10. Persistent protection from allergic disease was observed in the absence of IL-10, indicating the primary mechanism of PCF protection is IL-10 independent. Ex vivo and in vitro analysis of PCF-treated dendritic cells (DC) demonstrated reduced activation receptor expression and cytokine production in response to either RW or lipopolysaccharide stimulation. These findings extend previous studies that showed infection with A. suum alters expression of allergic disease and suggest that PCF can contribute to this effect by interference with DC function.
McConchie
Brittany W
BW
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, Twinbrook II Room 125, 12441 Parklawn Drive, Rockville, MD 20852, USA.
Norris
Hillary H
HH
Bundoc
Virgilio G
VG
Trivedi
Shweta
S
Boesen
Agnieszka
A
Urban
Joseph F
JF
Keane-Myers
Andrea M
AM
D031164:Ambrosia / Q000276:immunology; D000818:Animals; D052179:Antigens, Plant / Q000276:immunology; D017165:Ascaris suum / Q000276:immunology*; D001249:Asthma / Q000473:pathology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003233:Conjunctivitis, Allergic / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D007249:Inflammation / Q000517:prevention & control; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D011657:Pulmonary Eosinophilia / Q000517:prevention & control; D012130:Respiratory Hypersensitivity / Q000473:pathology / Q000517:prevention & control*; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology
D052179:Antigens, Plant; D016207:Cytokines; D008070:Lipopolysaccharides; D016753:Interleukin-10