Signaling through G{alpha}i2 protein is required for recruitment of neutrophils for antibody-mediated elimination of larval Strongyloides stercoralis in mice.
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.[1]References
- Signaling through G{alpha}i2 protein is required for recruitment of neutrophils for antibody-mediated elimination of larval Strongyloides stercoralis in mice. Padigel, U.M., Stein, L., Redding, K., Lee, J.J., Nolan, T.J., Schad, G.A., Birnbaumer, L., Abraham, D. J. Leukoc. Biol. (2007) [Pubmed]
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