Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs

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

doi:10.1128/mBio.02369-14

Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs

Journal Article · Tue Jan 06 00:00:00 EST 2015 · mBio (Online)

DOI:https://doi.org/10.1128/mBio.02369-14· OSTI ID:1201740

Kim, Hwan Keun ^[1]; Falugi, Fabiana ^[1]; Thomer, Lena ^[1]; Missiakas, Dominique M. ^[1]; Schneewind, Olaf ^[1]

Univ. of Chicago, IL (United States). Dept. of Microbiology; Argonne National Lab. (ANL), Argonne, IL (United States)

Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links V_H3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High V_H3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host B cell responses. Immunization with SpA_KKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1201740

Journal Information:: mBio (Online), Journal Name: mBio (Online) Journal Issue: 1 Vol. 6; ISSN 2150-7511

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

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