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Infection and Immunity, December 2003, p. 6835-6843, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6835-6843.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Specificity and Mechanism of Immunoglobulin M (IgM)- and IgG-Dependent Protective Immunity to Larval Strongyloides stercoralis in Mice

Jessica A. Ligas,1 Laura A. Kerepesi,1 Ann Marie Galioto,1 Sara Lustigman,2 Thomas J. Nolan,3 Gerhard A. Schad,3 and David Abraham1*

Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107,1 The Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10021,2 Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 191043

Received 25 June 2003/ Returned for modification 17 August 2003/ Accepted 18 September 2003

Protective immunity in mice to the infective third-stage larvae (L3) of Strongyloides stercoralis was shown to be dependent on immunoglobulin M (IgM), complement activation, and granulocytes. The objectives of the present study were to determine whether IgG was also a protective antibody isotype and to define the specificity and the mechanism by which IgG functions. Purified IgG recovered from mice 3 weeks after a booster immunization with live L3 was shown to transfer high levels of protective immunity to naïve mice. IgG transferred into mice treated to block complement activation or to eliminate granulocytes failed to kill the challenge larvae. Transfer of immune IgG into IL-5 knockout (KO) mice, which are deficient in eosinophils, resulted in larval attrition, while transfer into FcR{gamma} KO mice did not result in larval killing. These findings suggest that IgG from mice immunized with live L3 requires complement activation and neutrophils for killing of L3 through an antibody-dependent cellular cytotoxicity (ADCC) mechanism. This is in contrast to the results of investigations using IgM from mice immunized with live L3 and IgG from mice immunized with larval antigens soluble in deoxycholate in which protective immunity was shown to be ADCC independent. Western blot analyses with immune IgM and IgG identified few antigens recognized by all protective antibody isotypes. Results from immunoelectron microscopy demonstrated that the protective antibodies bound to different regions in the L3. It was therefore concluded that while IgM and IgG antibodies are both protective against larval S. stercoralis, they recognize different antigens and utilize different killing mechanisms.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, Thomas Jefferson University, 233 South 10th St., Philadelphia, PA 19107. Phone: (215) 503-8917. Fax: (215) 923-9248. E-mail: David.Abraham{at}jefferson.edu.

Editor: W. A. Petri, Jr.


Infection and Immunity, December 2003, p. 6835-6843, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6835-6843.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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