IL-10 Plays Opposing Roles during Staphylococcus aureus Systemic and Localized Infections

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 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 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.

Low cationicity is important for systemic in vivo efficacy of database-derived peptides against drug-resistant Gram-positive pathogens

“…While IL-17 can recruit neutrophils, IL-10 may neutralize TNF-α, attenuate tissue pathology, and reduce mortality (37). In addition, the balance between the IL-10 and IL-17 cytokines is also crucial for bacterial elimination and protecting the host from a pathological condition at the site of infection (38,39). These results depict a picture that DFT peptides play a critical role in eliminating S. aureus USA300 via direct killing as well as immune boosting both in vitro and in vivo.…”

A murine model of Staphylococcus aureus infected chronic diabetic wound: A new tool to develop alternative therapeutics

“…It is known that in the absence of effective microbial decontamination, prolonged inflammation may enter a chronic state prone to failure to heal . While IL‐10 plays an important protective role and is required to prevent bacterial spread, S 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 . The interactions between S aureus and IL‐10 promotion are complex, and further studies need to be undertaken.…”

“…The interactions between S aureus and IL‐10 promotion are complex, and further studies need to be undertaken. A high level of IL‐10 may facilitate bacterial persistence, whereas a low level of IL‐10 may cause excessive activation of immune cells and lead to fatal host‐mediated damages or bacterial superinfections . Since these cytokines may also facilitate the tissue‐healing process in injuries caused by infection or inflammation, they could be explored as an anti‐scarring therapeutic agent with potential application in the treatment of infected wound, associated with topical antimicrobial agents.…”

Toll-like receptor 2: An important immunomodulatory molecule during Helicobacter pylori infection

“…IL-10 contributes in pathologic events during acute localized S. aureus infection by inhibiting local proinflammatory cytokine production. However, during the acute systemic S. aureus infection, IL-10 via the same mechanism protects the host by controlling immunopathologic responses [126]. These findings represent that TLR2-related IL-10 production may play different or even opposing roles during systemic and localized S. aureus infections.…”

“…Staphylococcus aureus (S. aureus) induces the production of IL-10 by monocytes, macrophages and B1a cells in a TLR2-dependent manner [125,126]. IL-10 contributes in pathologic events during acute localized S. aureus infection by inhibiting local proinflammatory cytokine production.…”