Abstract |
The heterotrimeric guanine nucleotide- binding protein Galphai2 is involved in regulation of immune responses against microbial and nonmicrobial stimuli. Galphai2-/- mice have a selectively impaired IgM response consistent with a disorder in B cell development yet have augmented T cell effector function associated with increased production of IFN-gamma and IL-4. The goal of the present study was to determine if a deficiency in the Galphai2 protein in mice would affect the protective immune response against Strongyloides stercoralis, which is IL-4-, IL-5-, and IgM-dependent. Galphai2-/- and wild-type mice were immunized and challenged with S. stercoralis larvae and analyzed for protective immune responses against infection. Galphai2-/- mice failed to kill the larvae in the challenge infection as compared with wild-type mice despite developing an antigen-specific Th2 response characterized by increased IL-4, IL-5, IgM, and IgG. Transfer of serum collected from immunized Galphai2-/- mice to naïve wild-type mice conferred passive protective immunity against S. stercoralis infection thus confirming the development of a protective antibody response in Galphai2-/- mice. Differential cell analyses and myeloperoxidase assays for quantification of neutrophils showed a significantly reduced recruitment of neutrophils into the microenvironment of the parasites in immunized Galphai2-/- mice. However, cell transfer studies demonstrated that neutrophils from Galphai2-/- mice are competent in killing larvae. These data demonstrate that Galphai2 signaling events are not required for the development of the protective immune responses against S. stercoralis; however, Galphai2 is essential for the recruitment of neutrophils required for host-dependent killing of larvae.
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Authors | Udaikumar M Padigel, Louis Stein, Kevin Redding, James J Lee, Thomas J Nolan, Gerhard A Schad, Lutz Birnbaumer, David Abraham |
Journal | Journal of leukocyte biology
(J Leukoc Biol)
Vol. 81
Issue 4
Pg. 1120-6
(Apr 2007)
ISSN: 0741-5400 [Print] England |
PMID | 17242370
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Helminth
- GTP-Binding Protein alpha Subunit, Gi2
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Topics |
- Animals
- Antibodies, Helminth
(immunology)
- Cells, Cultured
- GTP-Binding Protein alpha Subunit, Gi2
(genetics, metabolism)
- Host-Parasite Interactions
- Immunity, Innate
- Larva
(immunology)
- Male
- Mice
- Neutrophils
(immunology, metabolism, physiology)
- Signal Transduction
- Strongyloides stercoralis
(immunology)
- Strongyloidiasis
(immunology)
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