IL-10 Plays Opposing Roles duringStaphylococcus aureusSystemic and Localized Infections.
IL-10 is a potent anti-inflammatory mediator that plays a crucial role in limiting host immunopathology during bacterial infections by controlling effector T cell activation.Staphylococcus aureushas previously been shown to manipulate the IL-10 response as a mechanism of immune evasion during chronic systemic and biofilm models of infection. In the present study, we demonstrate divergent roles for IL-10 depending on the site of infection. During acute systemicS. aureusinfection, IL-10 plays an important protective role and is required to prevent bacterial dissemination and host morbidity by controlling effector T cells and the associated downstream hyperactivation of inflammatory phagocytes, which are capable of host tissue damage. CD19+CD11b+CD5+B1a regulatory cells were shown to rapidly express IL-10 in a TLR2-dependent manner in response toS. aureus, and adoptive transfer of B1a cells was protective during acute systemic infection in IL-10-deficient hosts. In contrast, during localized s.c. infection, IL-10 production plays a detrimental role by facilitating bacterial persistence via the same mechanism of controlling proinflammatory T cell responses. Our findings demonstrate that induction of IL-10 has a major influence on disease outcome during acuteS. aureusinfection. Too much IL-10 at one end of the scale may suppress otherwise protective T cell responses, thus facilitating persistence of the bacteria, and at the other end, too little IL-10 may tend toward fatal host-mediated pathology through excessive activation of T cells and associated phagocyte-mediated damage.
Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; and.
John M
JM
Leech
Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; and.
Keenan A
0000-0002-9242-0170
KA
Lacey
Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; and.
Michelle E
0000-0002-0138-5630
ME
Mulcahy
Infection Immunology Research Group, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany.
Eva
E
Medina
Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; and rachel.mcloughlin@tcd.ie.
Rachel M
0000-0003-4553-018X
RM
McLoughlin
D000208:Acute Disease; D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology; D016470:Bacteremia / Q000150:complications / Q000276:immunology*; D018441:Biofilms; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010538:Peritonitis / Q000276:immunology* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000150:complications / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism
C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D016753:Interleukin-10