Signaling through Gαi2 protein is required for recruitment of neutrophils for antibody-mediated elimination of larval Strongyloides stercoralis in mice

Journal of Leukocyte Biology

Lutz Birnbaumer¹  David Abraham³  Gerhard A. Schad⁴  Thomas J. Nolan⁴  Kevin Redding³  Udaikumar M. Padigel³  Louis Stein³  James J. Lee² 

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

关键词: parasite;    heterotrimeric;    G protein;    cytokine;    antibody;   

DOI  :  10.1189/jlb.1106695

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown