Vancomycin Treatment Alters Humoral Immunity and Intestinal Microbiota in an Aged Mouse Model of Clostridium difficile Infection.

Background: The elderly host is highly susceptible to severe disease and treatment failure in Clostridium difficile infection (CDI). We investigated how treatment with vancomycin in the aged host influences systemic and intestinal humoral responses and select intestinal microbiota.

Methods: Young (age, 2 months) and aged (age, 18 months) C57BL/6 mice were infected with VPI 10463 after exposure to broad-spectrum antibiotics.

BAFF regulates follicular helper t cells and affects their accumulation and interferon-γ production in autoimmunity.

Objective: Follicular helper T (Tfh) cells are critical for the development of protective antibodies via germinal center (GC) B cell responses; however, uncontrolled Tfh cell expansion activates autoreactive B cells to produce antibodies that cause autoimmunity. The mechanisms that control Tfh cell homeostasis remain largely unknown. The aim of this study was to determine the contribution of BAFF to Tfh cell responses in autoimmunity.

Neutrophils contribute to excess serum BAFF levels and promote CD4+ T cell and B cell responses in lupus-prone mice.

Despite increased frequencies of neutrophils found in autoimmune diseases such as systemic lupus erythematosus (SLE), how they contribute to disease pathogenesis and the mechanisms that affect the accumulation of neutrophils are poorly understood. The aim of this study was to identify factors in autoantibody-mediated autoimmunity that controls the accumulation of spleen resident neutrophils and to determine whether neutrophils contribute to abnormal B cell responses. Increased levels of the cytokine BAFF have been linked to loss of B cell tolerance in autoimmunity, but the cellular source responsible for excess BAFF is unknown.

Dysregulated CD4+ T cells from SLE-susceptible mice are sufficient to accelerate atherosclerosis in LDLr-/- mice.

Objective: Accelerated atherosclerosis is a major source of morbidity in systemic lupus erythematosus (SLE). However, the cause of SLE-accelerated atherosclerosis remains unclear.

Methods: CD4(+) T cells from C57/Bl/6 (B6) or SLE-susceptible B6.

Mycophenolate mofetil but not atorvastatin attenuates atherosclerosis in lupus-prone LDLr(-/-) mice.

Rationale: Recent clinical and preclinical studies have demonstrated that systemic lupus erythematosus (SLE) is associated with an increased risk for cardiovascular disease (CVD). However, unlike in the general population, little is known regarding the efficacy of atheroprotective interventions in patients with SLE. The current study aims to determine the benefit of lymphocyte inhibition on reducing the atherosclerotic burden in SLE-susceptible LDLr-deficient mice.