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Published online before print January 22, 2007

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1106695

Received for publication November 23, 2006.
Revised November 23, 2006.
Accepted for publication December 20, 2006.

Article

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 ^*@

*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

^@ To whom correspondence should be addressed. E-mail: David.Abraham{at}jefferson.edu.

	Abstract

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: helminthes • parasite • infection • heterotrimeric • cytokine