[HTML][HTML] IL-10 plays opposing roles during Staphylococcus aureus systemic and localized infections

JM Leech, KA Lacey, ME Mulcahy… - The Journal of …, 2017 - journals.aai.org
JM Leech, KA Lacey, ME Mulcahy, E Medina, RM McLoughlin
The Journal of Immunology, 2017journals.aai.org
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 aureus has 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 systemic S. aureus infection, IL-10 plays an important protective role …
Abstract
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 aureus has 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 systemic S. aureus infection, 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 to S. aureus, and adoptive transfer of B1a cells was protective during acute systemic infection in IL-10–deficient hosts. In contrast, during localized sc 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 acute S. aureus infection. 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.
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