B-Cell-Deficient Mice Show an Exacerbated Inflammatory Response in a Model ofChlamydophila abortusInfection

Abstract

The resolution of Chlamydophila abortus (Chlamydia psittaci serotype 1) infection is dependent on gamma interferon and CD8؉ T cells, and classically, B cells have been considered to play a minimal role in host defense. The role of B cells in the immune response was studied by using a model of infection in mice with genetically modified immunoglobulin M transmembrane domains (MT). In the absence of B cells, infection with C. abortus leads to an acute severe fatal disease that involves a disseminated intravascular coagulation syndrome. MT mice displayed an increased level of proinflammatory cytokines in serum, and an increased number of neutrophils was observed in the lesions. The possible deleterious role of neutrophils in the pathogenesis of disease in MT mice was determined by depletion of the neutrophils with the monoclonal antibody RB6-8C5. This led to an enhancement of the bacterial burden and early mortality in both MT and wild-type mice, while necrotic lesions remained. Analysis of the presence of immunoregulatory cytokines showed significantly lower levels of transforming growth factor ␤ in the sera of MT mice. However, mice lacking mature B cells were able to establish a specific immune response that protected them from a secondary challenge. Taken together, these data suggest an immunomodulatory role for B cells in the early events of C. abortus primary infection that can protect mice against an exaggerated inflammatory response.

Signaling via the MyD88 Adaptor Protein in B Cells Suppresses Protective Immunity during Salmonella typhimurium Infection

“…MyD88 signaling in B cells also resulted in inhibition of this innate response upon rechallenge of vaccinated mice. Similarly, B cell-deficient mice mounted increased neutrophil responses after infection with Francisella tularensis, Chlamydophila abortus, Mycobacterium tuberculosis, or Leishmania donovani, which can all signal via TLRs and MyD88 (Bosio and Elkins, 2001;Buendía et al, 2002;Buendía et al, 2009;Maglione et al, 2007;Smelt et al, 2000). Although the signals driving B cell-mediated inhibitions of neutrophils were not defined in these studies, our observations together with these data suggest a general role for MyD88 signaling in B cells and for IL-10 in the regulation of neutrophil responses.…”

Regulation of immunity and autoimmunity by B cells

“…mMT mice infected with Chlamydophila abortus died of an acute disease characterized by a disseminated intravascular coagulation syndrome. This is associated with increased serum levels of proinflammatory cytokines along with significantly low levels of TGF-b production [29]. This result suggests that B cells can regulate an early immune response to C. abortus, allowing clearance of the infection but preventing the development of immune pathology.…”

Virulence ofPseudomonas aeruginosain a Murine Model of Gastrointestinal Colonization and Dissemination in Neutropenia

“…In an attempt to show the critical contribution of neutrophils to innate immune defense against P. aeruginosa after initial GI colonization, we tried to eliminate any potential Cy-induced GI mucosal damage and lymphopenia by using an alternative means of neutropenia induction. Neutrophil depletion by monoclonal antibody treatment (RB6-8C5 MAb) has been used in number of animal models of infection (7,9,12,43,51). RB6-8C5 MAb reacts with a common epitope on Ly-6G and Ly-6C, previously known as the myeloid differentiation antigen Gr-1 (19).…”