title: The impact of Staphylococcus aureus-associated molecular patterns on staphylococcal superantigen-induced toxic shock syndrome and pneumonia.
abstract: Staphylococcus aureus is capable of causing a spectrum of human illnesses. During serious S. aureus infections, the staphylococcal pathogen-associated molecular patterns (PAMPs) such as peptidoglycan, lipoteichoic acid, and lipoproteins and even intact S. aureus, are believed to act in conjunction with the staphylococcal superantigens (SSAg) to activate the innate and adaptive immune system, respectively, and cause immunopathology. However, recent studies have shown that staphylococcal PAMPs could suppress inflammation by several mechanisms and protect from staphylococcal toxic shock syndrome, a life-threatening systemic disease caused by toxigenic S. aureus. Given the contradictory pro- and anti-inflammatory roles of staphylococcal PAMPs, we examined the effects of S. aureus-derived molecular patterns on immune responses driven by SSAg in vivo using HLA-DR3 and HLA-DQ8 transgenic mice. Our study showed that neither S. aureus-derived peptidoglycans (PGN), lipoteichoic acid (LTA), nor heat-killed Staphylococcus aureus (HKSA) inhibited SSAg-induced T cell proliferation in vitro. They failed to antagonize the immunostimulatory effects of SSAg in vivo as determined by their inability to attenuate systemic cytokine/chemokine response and reduce SSAg-induced T cell expansion. These staphylococcal PAMPs also failed to protect HLA-DR3 as well as HLA-DQ8 transgenic mice from either SSAg-induced toxic shock or pneumonia induced by a SSAg-producing strain of S. aureus.
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Ashenafi Y
authors.identifier: 0000-0002-9353-0005
authors.initials: AY
authors.lastname: Tilahun
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Melissa
authors.identifier: 0000-0001-6021-4033
authors.initials: M
authors.lastname: Karau
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Alessandro
authors.identifier: 0000-0003-4093-2972
authors.initials: A
authors.lastname: Ballard
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Miluka P
authors.identifier: 0000-0003-2166-1046
authors.initials: MP
authors.lastname: Gunaratna
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Anusa
authors.identifier: 0000-0001-9486-8350
authors.initials: A
authors.lastname: Thapa
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Chella S
authors.initials: CS
authors.lastname: David
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA ; Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Robin
authors.identifier: 0000-0001-6344-4141
authors.initials: R
authors.lastname: Patel
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA ; Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55905, USA ; Department of Immunology and Division of Infectious Diseases, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN 55905, USA.
authors.forename: Govindarajan
authors.identifier: 0000-0003-2608-8162
authors.initials: G
authors.lastname: Rajagopalan
mesh_terms: D000818:Animals; D006683:HLA-DQ Antigens / Q000235:genetics; D015803:HLA-DR3 Antigen / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008822:Mice, Transgenic; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D012772:Shock, Septic / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity*; D018089:Superantigens / Q000276:immunology*
chemical_list: D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D015803:HLA-DR3 Antigen; D018089:Superantigens