title: CD4+ T cells and CXC chemokines modulate the pathogenesis of Staphylococcus aureus wound infections.
abstract: T cells are critical for the formation of intraabdominal abscesses by Staphylococcus aureus. We hypothesized that T cells modulate the development of experimental staphylococcal infections by controlling polymorphonuclear leukocyte (PMN) trafficking. In models of staphylococcal s.c. abscess formation, hindpaw infection, and surgical wound infection, S. aureus multiplied in the tissues of WT C57BL/6J mice and elicited a marked inflammatory response. CD4(+) alphabeta T cells homed to the surgical wound infection site of WT animals. In contrast, significantly fewer S. aureus were recovered from the tissues of mice deficient in alphabeta T cells, and the inflammatory response was considerably diminished compared with that of WT animals. Alphabeta T cell receptor (-/-) mice had significantly lower concentrations of PMN-specific CXC chemokines in wound tissue than did WT mice. The severity of the wound infection was enhanced by administration of a CXC chemokine and abrogated by antibodies that blocked the CXC receptor. An acapsular mutant was less virulent than the parental S. aureus strain in both the s.c. abscess and the surgical wound infection models in WT mice. These data reveal an important and underappreciated role for CD4(+) alphabeta T cells in S. aureus infections in controlling local CXC chemokine production, neutrophil recruitment to the site of infection, and subsequent bacterial replication.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: McLoughlin
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Solinga
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Rich
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Zaleski
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115.
authors.forename: Jordan L
authors.initials: JL
authors.lastname: Cocchiaro
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115.
authors.forename: Allison
authors.initials: A
authors.lastname: Risley
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115.
authors.forename: Arthur O
authors.initials: AO
authors.lastname: Tzianabos
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115 jean.lee@channing.harvard.edu.
authors.forename: Jean C
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002465:Cell Movement; D019743:Chemokines, CXC / Q000276:immunology*; D004195:Disease Models, Animal; D006614:Hindlimb / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013207:Staphylococcal Skin Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D013211:Staphylococcus aureus / Q000378:metabolism / Q000502:physiology*; D013530:Surgical Wound Infection / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology
chemical_list: D019743:Chemokines, CXC