Peptidoglycan-linked protein A promotes T cell-dependent antibody expansion during Staphylococcus aureus infection.

Abstract

A hallmark of Staphylococcus aureus disease in humans is persistent infections without development of protective immune responses. Infected patients generate VH3 plasmablast expansions and increased VH3 idiotype Ig; however, the mechanisms for staphylococcal modification of immune responses are not known. We report here that S. aureus-infected mice generate VH3 antibody expansions via a mechanism requiring MHC-restricted antigen presentation to CD4(+) T cells and staphylococcal protein A (SpA), a cell wall-anchored surface molecule that binds Fcγ and VH3 variant heavy chains of Ig. VH3 expansion occurred with peptidoglycan-linked SpA from the bacterial envelope but not with recombinant SpA, and optimally required five tandem repeats of its Ig-binding domains. Signaling via receptor-interacting serine/threonine protein kinase 2 (RIPK2) was essential for implementing peptidoglycan-linked SpA superantigen activity. VH3 clan IgG from S. aureus-infected or SpA-treated animals was not pathogen-specific, suggesting that SpA cross-linking of VH3 idiotype B-cell receptors and activation via attached peptidoglycan are the determinants of staphylococcal escape from adaptive immune responses.

• Authors: Hwan Keun Kim, Fabiana Falugi, Dominique M Missiakas, Olaf Schneewind
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 113 Issue 20 Pg. 5718-23 (May 17 2016) ISSN: 1091-6490 [Electronic] United States
• PMID: 27140614 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bacterial
• Peptidoglycan
• Staphylococcal Protein A

Topics

• Animals
• Antibodies, Bacterial (biosynthesis, blood)
• Antibody Formation
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Peptidoglycan (immunology)
• Staphylococcal Infections (blood, immunology, microbiology)
• Staphylococcal Protein A (immunology)
• Staphylococcus aureus (immunology)
• T-Lymphocytes (immunology, metabolism, microbiology)