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Infection and Immunity, October 2000, p. 5645-5651, Vol. 68, No. 10
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

B-Cell Deficiency Predisposes Mice to Disseminating Anaerobic Infections: Protection by Passive Antibody Transfer

Linda Hou, Hajime Sasakj, and Philip Stashenko*

Department of Cytokine Biology, Forsyth Institute, Boston, Massachusetts 02115

Received 23 February 2000/Returned for modification 12 April 2000/Accepted 30 June 2000

We have previously demonstrated that a high proportion of RAG-2 SCID knockout mice, which lack T and B cells, develop orofacial abscesses and disseminated infections following pulpal infection, whereas immunocompetent control mice do not. In the present study, we sought to identify the components of the adaptive immune response which contribute to protection against disseminating anaerobic infections and sepsis. For this purpose, various genetically engineered immunodeficient mice were employed, including RAG-2 SCID, Igh-6 (B-cell deficient), Tcrb Tcrd (T-cell deficient) and Hc0 (C5 deficient). For abscess induction, the mandibular first molars were subjected to pulp exposure on day 0. Teeth were infected with a mixture of four anaerobic pathogens, including Prevotella intermedia, Streptococcus intermedius, Fusobacterium nucleatum, and Peptostreptococcus micros, and teeth were sealed to prevent communication with the oral cavity. The findings demonstrate that both RAG-2 SCID and B-cell-deficient mice, but not T-cell- or C5-deficient mice, have increased susceptibility to the development of disseminating anaerobic infections. Abscess-susceptible RAG-2 SCID and B-cell-deficient mice also showed a significant loss of body weight, splenomegaly, and absent antibacterial antibody production. Furthermore, dissemination was significantly reduced, from 74 to 25%, in susceptible RAG-2 mice by passively transferred antibody, predominantly immunoglobulin G2b (IgG2b) and IgM, against the infecting bacterial innoculum. Fractionated IgG-enriched preparations were more efficient in transferring protection than IgM preparations. We conclude that an antibody-mediated mechanism(s), most likely bacterial opsonization, is of importance in localizing anaerobic root canal infections and in preventing their systemic spread.

* Corresponding author. Mailing address: Department of Cytokine Biology, Forsyth Institute, 140 The Fenway, Boston, MA 02115. Phone: (617) 262-5200. Fax: (617) 262-4021. E-mail: pstashenko{at}forsyth.org.

Infection and Immunity, October 2000, p. 5645-5651, Vol. 68, No. 10
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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