Protein A Suppresses Immune Responses during Staphylococcus aureus Bloodstream Infection in Guinea Pigs

Hwan Keun Kim, Fabiana Falungi, Lena Thomer, Dominique M. Missiakas, Olaf Schneewind

mBio Jan, 2015; 6(1): e02369-14

Speaker: Kuang-Yu Chen (陳冠宇)               Time: 15:00~16:00, Dec. 16, 2015

Commentator: Dr. Pei-Jane Tsai (蔡佩珍教授)      Place: Room 601

Abstract:

        Staphylococcus aureus is a commensal of human skin and an invasive pathogen causing skin and soft tissue infections, bacteremia, sepsis and endocarditis. Work on staphylococcal vaccines commenced more than a century ago, and it may have failed because human Ig effector function are modified by staphylococcal protein A ( SpA). SpA is expressed by all clinical S. aureus isolates. The immunosuppressive attributes of SpA have been ascribed to two distinct binding activities for human and animal Igs. SpA binding to the Fcγ domain of IgG blocks opsonophagocytosis (OPK) of staphylocci¹, whereas SpA binding to Fab and crosslinking of IgM promotes B cell superantigen activity². Nontoxigenic SpA, designated SpA_KKAA, associate with Ig Fcγ and Fab. The SpA-derived antibodies promotes human immune response to a wide spectrum of antigens. Since protective immunity against S. aureus infection cannot be detected when using mice model, the authors used guinea pigs as an infection model. Results showed that guinea pigs infected with S. aureus elaborate VH3 clan IgG and IgM with high abundance, similar to the human immune system. Next, guinea pigs injected with SpA KKAA absorbed to aluminum hydroxide raises protein A-specific antibodies that can protect against S. aureus infection. The authors concluded that these studies established guinea pigs as a model for S. aureus bloodstream infection which may be used for vaccine development and preclinical efficacy studies.

References:

1   Forsgren, A. & Quie, P. G. Effects of staphylococcal protein A on heat labile opsonins. J Immunol 112, 1177-1180 (1974).

2   Goodyear, C. S. & Silverman, G. J. Death by a B cell superantigen: In vivo VH-targeted apoptotic supraclonal B cell deletion by a Staphylococcal Toxin. J Exp Med 197, 1125-1139, doi:10.1084/jem.20020552 (2003).