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Ten Weeks of Infection with a Tissue-Invasive Helminth Protects against Local Immune Complex-Mediated Inflammation, but Not Cutaneous Type I Hypersensitivity, in Previously Sensitized Mice.

Abstract
In this study, we evaluated the effect chronic helminth infection has on allergic disease in mice previously sensitized to OVA. Ten weeks of infection with Litomosoides sigmodontis reduced immunological markers of type I hypersensitivity, including OVA-specific IgE, basophil activation, and mast cell degranulation. Despite these reductions, there was no protection against immediate clinical hypersensitivity following intradermal OVA challenge. However, late-phase ear swelling, due to type III hypersensitivity, was significantly reduced in chronically infected animals. Levels of total IgG2a, OVA-specific IgG2a, and OVA-specific IgG1 were reduced in the setting of infection. These reductions were most likely due to increased Ab catabolism as ELISPOT assays demonstrated that infected animals do not have suppressed Ab production. Ear histology 24 h after challenge showed infected animals have reduced cellular infiltration in the ear, with significant decreases in numbers of neutrophils and macrophages. Consistent with this, infected animals had less neutrophil-specific chemokines CXCL-1 and CXCL-2 in the ear following challenge. Additionally, in vitro stimulation with immune complexes resulted in significantly less CXCL-1 and CXCL-2 production by eosinophils from chronically infected mice. Expression of FcγRI was also significantly reduced on eosinophils from infected animals. These data indicate that chronic filarial infection suppresses eosinophilic responses to Ab-mediated activation and has the potential to be used as a therapeutic for pre-existing hypersensitivity diseases.
AuthorsHolly Evans, Kristin E Killoran, Blima K Mitre, C Paul Morris, So-Young Kim, Edward Mitre
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 195 Issue 7 Pg. 2973-84 (Oct 01 2015) ISSN: 1550-6606 [Electronic] United States
PMID26324775 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
CopyrightCopyright © 2015 by The American Association of Immunologists, Inc.
Chemical References
  • Antigen-Antibody Complex
  • Chemokine CXCL1
  • Chemokine CXCL2
  • Cxcl1 protein, mouse
  • Cxcl2 protein, mouse
  • Fcgr1 protein, mouse
  • Immunoglobulin G
  • Receptors, IgG
  • Immunoglobulin E
  • Ovalbumin
Topics
  • Animals
  • Antigen-Antibody Complex (immunology)
  • Basophils (immunology)
  • Cell Degranulation (immunology)
  • Chemokine CXCL1 (metabolism)
  • Chemokine CXCL2 (metabolism)
  • Dermatitis, Contact (immunology)
  • Ear (physiology)
  • Eosinophils (immunology)
  • Female
  • Filariasis (immunology, parasitology)
  • Filarioidea (immunology)
  • Gerbillinae
  • Hypersensitivity, Immediate (immunology)
  • Immune Complex Diseases (immunology)
  • Immunoglobulin E (immunology)
  • Immunoglobulin G (blood, immunology)
  • Immunosuppression Therapy
  • Inflammation (immunology)
  • Leukocyte Count
  • Macrophages (immunology)
  • Mast Cells (immunology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Neutrophils (immunology)
  • Ovalbumin (immunology)
  • Receptors, IgG (biosynthesis)

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