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Published online before print January 22, 2007

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(Journal of Leukocyte Biology. 2007;81:1120-1126.)
© 2007 by Society for Leukocyte Biology

Signaling through Gi2 protein is required for recruitment of neutrophils for antibody-mediated elimination of larval Strongyloides stercoralis in mice

Udaikumar M. Padigel^*, Louis Stein^*, Kevin Redding^*, James J. Lee, Thomas J. Nolan, Gerhard A. Schad, Lutz Birnbaumer and David Abraham^*,1

^* Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA;
Department of Biochemistry and Molecular Biology, Mayo Clinic, Scottsdale, Arizona, USA;
Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA; and
National Institute of Environmental Health Sciences (NIEHS), Laboratory of Signal Transduction, Research Triangle Park, North Carolina, USA

¹ Correspondence: Department of Microbiology and Immunology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA. E-mail: david.abraham{at}jefferson.edu

The heterotrimeric guanine nucleotide-binding protein Gi2 is involved in regulation of immune responses against microbial and nonmicrobial stimuli. Gi2^–/– 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- and IL-4. The goal of the present study was to determine if a deficiency in the Gi2 protein in mice would affect the protective immune response against Strongyloides stercoralis, which is IL-4-, IL-5-, and IgM-dependent. Gi2^–/– and wild-type mice were immunized and challenged with S. stercoralis larvae and analyzed for protective immune responses against infection. Gi2^–/– 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 Gi2^–/– mice to naïve wild-type mice conferred passive protective immunity against S. stercoralis infection thus confirming the development of a protective antibody response in Gi2^–/– 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 Gi2^–/– mice. However, cell transfer studies demonstrated that neutrophils from Gi2^–/– mice are competent in killing larvae. These data demonstrate that Gi2 signaling events are not required for the development of the protective immune responses against S. stercoralis; however, Gi2 is essential for the recruitment of neutrophils required for host-dependent killing of larvae.

Key Words: parasite • heterotrimeric • G protein • cytokine • antibody