title: Subcutaneous infection with S. aureus in mice reveals association of resistance with influx of neutrophils and Th2 response.
abstract: Staphylococcus aureus is the leading cause of bacterial skin infection. Once it overcomes the epithelial barrier, it either remains locally controlled or spreads in the dermis causing soft tissue infection. These different courses depend not only on its virulence factors, but also on the immune response of the infected individual. The goal of this study was to identify host factors that influence different outcomes. We, therefore, established comparative analysis of subcutaneous footpad infection with S. aureus (SH1000) in different inbred mouse strains. We found that C57BL/6 mice are more susceptible than BALB/c and DBA/2 mice, reflected by significantly higher footpad swelling and bacterial load, as well as increased dissemination of bacteria into inguinal lymph nodes and kidneys. This susceptibility was associated with lower influx of polymorphonuclear leukocytes (PMNs), but higher secretion of CXCL-2. Remarkably, resistance correlated with S. aureus-specific Th2-cell response in BALB/c and DBA/2 mice, whereas susceptible C57BL/6 mice generated a Th1-cell response. As Th1 cells are able to induce release of CXCL-2, and as CXCL-2 is able to increase the survival of S. aureus within PMNs, interactions between PMNs and Th1 or Th2 cells need to be considered as important mechanisms of resistance in murine soft tissue infection with S. aureus.
authors.affiliation: Institute of Immunology, University of Muenster, Muenster, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Nippe
authors.forename: Georg
authors.initials: G
authors.lastname: Varga
authors.forename: Dirk
authors.initials: D
authors.lastname: Holzinger
authors.forename: Bettina
authors.initials: B
authors.lastname: Löffler
authors.forename: Eva
authors.initials: E
authors.lastname: Medina
authors.forename: Karsten
authors.initials: K
authors.lastname: Becker
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.forename: Jan M
authors.initials: JM
authors.lastname: Ehrchen
authors.forename: Cord
authors.initials: C
authors.lastname: Sunderkötter
mesh_terms: D000208:Acute Disease; D000818:Animals; D054360:Chemokine CXCL1 / Q000276:immunology / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology*; D013045:Species Specificity; D013207:Staphylococcal Skin Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D050151:Subcutaneous Fat / Q000276:immunology / Q000382:microbiology*; D018417:Th1 Cells / Q000276:immunology / Q000382:microbiology; D018418:Th2 Cells / Q000276:immunology / Q000382:microbiology*
chemical_list: D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse