Signaling through Gαi2 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, David Abraham

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1120-1126
Number of pages7
JournalJournal of Leukocyte Biology
Volume81
Issue number4
DOIs
StatePublished - Apr 2007

Fingerprint

Strongyloides stercoralis
Neutrophil Infiltration
Antibodies
Proteins
Larva
Interleukin-4
Immunoglobulin M
Interleukin-5
Neutrophils
Infection
Guanine Nucleotides
Peroxidase
Antibody Formation
Immunity
Carrier Proteins
Parasites
B-Lymphocytes
Immunoglobulin G

Keywords

  • Antibody
  • Cytokine
  • G protein
  • Heterotrimeric
  • Parasite

ASJC Scopus subject areas

  • Cell Biology

Cite this

Signaling through Gαi2 protein is required for recruitment of neutrophils for antibody-mediated elimination of larval Strongyloides stercoralis in mice. / Padigel, Udaikumar M.; Stein, Louis; Redding, Kevin; Lee, James J.; Nolan, Thomas J.; Schad, Gerhard A.; Birnbaumer, Lutz; Abraham, David.

In: Journal of Leukocyte Biology, Vol. 81, No. 4, 04.2007, p. 1120-1126.

Research output: Contribution to journalArticle

Padigel, Udaikumar M. ; Stein, Louis ; Redding, Kevin ; Lee, James J. ; Nolan, Thomas J. ; Schad, Gerhard A. ; Birnbaumer, Lutz ; Abraham, David. / Signaling through Gαi2 protein is required for recruitment of neutrophils for antibody-mediated elimination of larval Strongyloides stercoralis in mice. In: Journal of Leukocyte Biology. 2007 ; Vol. 81, No. 4. pp. 1120-1126.
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AU - Lee, James J.

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AB - 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.

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