The Rockefeller University

The human immune response to Staphylococcus aureus

Purpose

Staphylococcus aureus (SA) is a leading cause of morbidity mortality and as a result it is responsible for a marked economic burden on today?s health care system. Infections with SA that are resistant to Methicillin antibiotic (MRSA) are very common and are a major part of this burden. 30% the population are colonized with S. aureus so at least theoretically their immune system is constantly exposed to the bacteria and expected to induce protective immunity. However at the same time 30% the population experiencing an infection with S. aureus will be afflicted with recurrent infections with this bacterium and despite previous exposure. Developing a vaccine would be an ideal solution for prevention of these infections. However despite intensive study in the last 3 decades a successful vaccine against S.aureus is still unavailable. For developing and designing an efficient vaccine a better understanding of the immune response to S. aureus is needed..For many yearsthe concept was that B cell responses and antibody production are enough for protection against S.aureus. In recent years direct evidence from KO mice as well as evidence from humans with primary immune deficiency demonstrates that CD4 Th1 and Th17 immune responses are necessary for protection from S. aureus. Nevertheless our recent results demonstrate that the Th1 and Th17 response to the various S. aureus strains varied extensively in response to in-vitro stimulation. Further wide variability was also inspected in IgG expression by proliferating B cells in response to the different strains. We could show that mobile genetic elements carried by phages are responsible for a significant portion of this immune response variability. These findings are bringing up the possibility that the strain specificity is a new factor that might need to be taken into account when we are evaluating protection. At this time point what is not known/understood and what we want to clarify in the current study is: (i) Whether previous exposure to various strains results in different level of protective memory. (ii) How immune memory induced by exposure to one strain affect the ability to respond to other strains of S. aureus.

Condition

• Staphylococcus aureus