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 G alpha i2 is involved in regulation of immune responses against microbial and nonmicrobial stimuli. G alpha i2(-/-) 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 G alpha i2 protein in mice would affect the protective immune response against Strongyloides stercoralis, which is IL-4-, IL-5-, and IgM-dependent. G alpha i2(-/-) and wild-type mice were immunized and challenged with S. stercoralis larvae and analyzed for protective immune responses against infection. G alpha i2(-/-) 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 G alpha i2(-/-) mice to naive wild-type mice conferred passive protective immunity against S. stercoralis infection thus confirming the development of a protective antibody response in G alpha i2(-/-) mice. Differential cell analyses and mycloperoxidase assays for quantification of neutrophils showed a significantly reduced recruitment of nentrophils into the microenvironment of the parasites in immunized G alpha i2(-/-) mice. However, cell transfer studies demonstrated that nentrophils from G alpha i2(-/-) mice are competent in killing larvae. These data demonstrate that G alpha i2 signaling events are not required for the development of the protective immune responses against S. stercoralis; however, G alpha i2 is essential for the recruitment of neutrophils required for host-dependent killing of larvae.