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

Abstract

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 Hc 0 (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.Bacterial infection of the dental pulp occurs as a consequence of caries, trauma, and operative dental procedures. These infections are mixed and anaerobic in nature, and are associated with high morbidity and mortality if bacterial dissemination occurs from the root canal into the tissues or the circulation. In this regard, pulpal infections may cause cellulitis, are the most common source of infecting microorganisms in Ludwig's angina (15), and have been implicated in cavernous sinus thrombosis, brain abscesses, mediastinitis, and osteomyelitis (7,14). Oral bacteria are also a primary source of infections in transplant patients (13) and in immunodeficient and immunosuppressed individuals (22).Pulpal infections induce local immune responses in the periapical region surrounding the root of the tooth. This response consists of a typical mixed inflammatory infiltrate and is composed of T cells, B cells, plasma cells, macrophages, and neutrophils (21,23,31,32). However, it is unknown which of these responses protect the host against bacterial egress and dissemination. In previous studies, we developed a model of induced pulpal infection in RAG-2 severe combined immunodeficient (SCID) mice (34). RAG-2 SCID mice were foun...

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