Abstract
The heterotrimeric guanine nucleotide-binding protein Gαi2 is involved in regulation of immune responses against microbial and nonmicrobial stimuli. Gαi2+/+ 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-γ and IL-4. The goal of the present study was to determine if a deficiency in the Gαi2 protein in mice would affect the protective immune response against Strongyloides stercoralis, which is IL-4-, IL-5-, and IgM-dependent. Gαi2-/- and wild-type mice were immunized and challenged with S. stercoralis larvae and analyzed for protective immune responses against infection. Gαi2-/- 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 Gαi2-/- mice to naïve wild-type mice conferred passive protective immunity against S. stercoralis infection thus confirming the development of a protective antibody response in Gαi2-/- 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 Gαi2-/- mice. However, cell transfer studies demonstrated that neutrophils from Gαi2-/- mice are competent in killing larvae. These data demonstrate that Gαi2 signaling events are not required for the development of the protective immune responses against S. stercoralis; however, Gαi2 is essential for the recruitment of neutrophils required for host-dependent killing of larvae.
Original language | English (US) |
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Pages (from-to) | 1120-1126 |
Number of pages | 7 |
Journal | Journal of Leukocyte Biology |
Volume | 81 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2007 |
Keywords
- Antibody
- Cytokine
- G protein
- Heterotrimeric
- Parasite
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Cell Biology