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Bisphosphonate effect on murine whole draining lymph nodes before and 8 hours after VSV infection

ABSTRACT: Bisphosphonates are a class of drugs that are widely used to inhibit loss of bone mass in patients. We show that the administration of clinically relevant doses of bisphosphonates in mice increases antibody responses to live and inactive viruses, proteins, haptens and existing commercial vaccine formulations. Bisphosphonates exert this adjuvant-like activity in the absence of CD4+ and γδ T cells, neutrophils or dendritic cells and their effect does not rely on local macrophage depletion nor does it depend upon Toll-like receptor signaling or the inflammasome. Rather, bisphosphonates target directly B cells and enhance B cell expansion and antibody production upon antigen encounter. These data establish bisphosphonates as a novel class of adjuvants that boost humoral immune responses. Of note, gene-expression profile analysis shows that bisphosphonate treatment up-regulates a number of B cell-specific transcripts and gene sets associated with B cell function, suggesting that bisphosphonates might directly target B cells. C57Bl/6 mice received intrafoodpad injections of Clodronate (CLD, 2mg) or vehicle control (PBS) 3 and 1 day prior to infection with VSV serotype Indiana in the same footpad. Popliteal lymph nodes were harvested immediately before or 8 hours after the infection. Total RNA was extracted and prepared for hybridization on Affymetrix microarrays.

ORGANISM(S): Mus musculus

SUBMITTER: Elena Tonti

PROVIDER: E-GEOD-50403 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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