Title:Short Term, Low Dose Simvastatin Pretreatment Alters Memory Immune Function Following Secondary Staphylococcus aureus Infection
Volume: 17
Issue: 10
Author(s): Lisa K. Smelser, Callum Walker, Erin M. Burns, Michael Curry, Nathanael Black, Jennifer A. Metzler, Susan A. McDowell and Heather A. Bruns
Affiliation:
Keywords:
Immune response, memory, secondary infection, sepsis, S. aureus, statin.
Abstract: Statins are potent modulators of immune responses, resulting in their ability to enhance host
survival from primary bacterial infections. Alterations in primary immune responses that may be beneficial
for survival following infection may also result in alterations in the generation of the immunologic
memory response and subsequently affect immune responses mounted during secondary bacterial
infection. In this study, we report that levels of total serum IgG2c, following primary infection,
were decreased in simvastatin pretreated mice, and investigate the effect of simvastatin treatment,
prior to primary infection, on immune responses activated during secondary S. aureus infection. A
secondary infection model was implemented whereby simvastatin pretreated and control mice were reinfected
with S. aureus 14 days after primary infection, with no additional simvastatin treatment, and assessed for survival
and alterations in immune function. While survivability to secondary S. aureus infection was not different between simvastatin
pretreated and control mice, memory B and T lymphocyte functions were altered. Memory B cells, isolated 14
days after secondary infection, from simvastatin pretreated mice and stimulated ex vivo produced increased levels of IgG1
compared to memory B cells isolated from control mice, while levels of IgM and IgG2c remained similar. Furthermore,
memory B and T lymphocytes from simvastatin pretreated mice exhibited a decreased proliferative response when stimulated
ex vivo compared to memory cells isolated from control mice. These findings demonstrate the ability of a short term,
low dose simvastatin treatment to modulate memory immune function.
