title: The Staphylococcus aureus Map protein is an immunomodulator that interferes with T cell-mediated responses.
abstract: Staphylococcus aureus (SA) is an opportunistic pathogen that affects a variety of organ systems and is responsible for many diseases worldwide. SA express an MHC class II analog protein (Map), which may potentiate SA survival by modulating host immunity. We tested this hypothesis in mice by generating Map-deficient SA (Map(-)SA) and comparing disease outcome to wild-type Map(+)SA-infected mice. Map(-)SA-infected mice presented with significantly reduced levels of arthritis, osteomyelitis, and abscess formation compared with control animals. Furthermore, Map(-)SA-infected nude mice developed arthritis and osteomyelitis to a severity similar to Map(+)SA-infected controls, suggesting that T cells can affect disease outcome following SA infection and Map may attenuate cellular immunity against SA. The capacity of Map to alter T cell function was tested more specifically in vitro and in vivo using native and recombinant forms of Map. T cells or mice treated with recombinant Map had reduced T cell proliferative responses and a significantly reduced delayed-type hypersensitivity response to challenge antigen, respectively. These data suggest a role for Map as an immunomodulatory protein that may play a role in persistent SA infections by affecting protective cellular immunity.
authors.affiliation: The Center for Extracellular Matrix Biology, Texas A&M University System Health Science Center, Albert B. Alkek Institute of Biosciences and Technology, Houston, Texas 77030-7552, USA.
authors.forename: Lawrence Y
authors.initials: LY
authors.lastname: Lee
authors.forename: Yuko J
authors.initials: YJ
authors.lastname: Miyamoto
authors.forename: Bradley W
authors.initials: BW
authors.lastname: McIntyre
authors.forename: Magnus
authors.initials: M
authors.lastname: Höök
authors.forename: Kirk W
authors.initials: KW
authors.lastname: McCrea
authors.forename: Damien
authors.initials: D
authors.lastname: McDevitt
authors.forename: Eric L
authors.initials: EL
authors.lastname: Brown
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis; D001170:Arthritis, Infectious / Q000209:etiology / Q000276:immunology / Q000473:pathology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D010019:Osteomyelitis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; C095564:Map protein, Staphylococcus aureus; D011994:Recombinant Proteins