Neutrophils in innate host defense against Staphylococcus aureus infections

Rigby, Kevin M.; DeLeo, Frank R.

doi:10.1007/s00281-011-0295-3

Cited by 337 publications

(318 citation statements)

References 293 publications

(318 reference statements)

Supporting

Mentioning

307

Contrasting

Unclassified

Order By: Relevance

“…In the absence of IL-10, there was a significant expansion of IL-17-producing gd + T cells locally at 3 h postinfection as compared with that observed in WT mice. IL-17 can directly control neutrophil activation (35) and, consistent with this, neutrophils produced greater amounts of ROS in the absence of IL-10. Additionally, IFN-g-producing Th1 cells were also significantly elevated in IL-10 2/2 mice on day 7 compared with WT mice.…”

Section: Discussionmentioning

confidence: 58%

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

Leech

Lacey

Mulcahy

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 58%

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

Leech

Lacey

Mulcahy

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Host immunity to both local and systemic MRSA infections depends on neutrophil chemotaxis to sites of infection (45,65); in the kidney, abscess formation results in the "walling off" of discrete foci of pathogenic infiltrate by initially surrounding bacteria with an eosinophilic pseudocapsule (66) with subsequent neutrophil recruitment to surround the pseudocapsule (36). The overall size of the abscess can be limited by fibrin deposits that serve to partition areas of inflammation from healthy tissue (67).…”

Section: Discussionmentioning

confidence: 99%

“…Neutrophils play a crucial role in the clearance of S. aureus from infected tissue. In addition to neutrophil phagocytosis of S. aureus, release of antimicrobial proteins (44), and oxidative killing of bacteria (45), neutrophil recruitment to sites of infection serves to wall off bacteria from healthy tissue, resulting in the formation of abscesses (46). Based on the importance of neutrophils to clearance of S. aureus infection and the immunofluorescence data suggesting that exposure to propofol dramatically increased neutrophil recruitment to the kidney during MRSA infection ( Fig.…”

mentioning

confidence: 99%

Propofol Sedation Exacerbates Kidney Pathology and Dissemination of Bacteria during Staphylococcus aureus Bloodstream Infections

Visvabharathy

Freitag

2017

Infect Immun

View full text Add to dashboard Cite

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for large numbers of postsurgical nosocomial infections across the United States and worldwide. Propofol anesthesia is widely used in surgery and in intensive care units, and recent evidence indicates that even brief exposure to propofol can substantially increase host susceptibility to microbial infection. Here, we delineate the impact of propofol sedation on MRSA bloodstream infections in mice in the presence and absence of prophylactic antibiotic treatment. Consistent with previous reports, brief periods of anesthesia with propofol were sufficient to significantly increase bacterial burdens and kidney pathology in mice infected with MRSA. Propofol exposure increased neutrophilic infiltrates into the kidney and enhanced bacterial dissemination throughout kidney tissue. Propofol sedation reduced populations of effector phagocytes and mature dendritic cells within the kidney and led to the apparent expansion of myeloid-derived suppressor cell-like populations. When propofol was coadministered with vancomycin prophylaxis, it dramatically increased kidney abscess formation and bacterial dissemination throughout kidney tissue at early times post-S. aureus infection compared to antibiotic-treated but nonsedated animals. Taken together, our data indicate that short-term sedation with propofol significantly increases the severity of bloodstream MRSA infection, even when administered in conjunction with vancomycin prophylaxis.KEYWORDS MRSA, anesthesia, bacterial pathogenesis, immune suppression, kidney abscess, macrophages, monocytes, vancomycin N osocomial infections are common complications that follow surgery or prolonged stays in intensive care units (ICU) of hospitals (1-5) and which result in large increases in patient morbidity and mortality in addition to elevated health care costs (6). The causative agents of nosocomial infection are often bacteria (4, 7), and Staphylococcus aureus is one of the most frequently isolated pathogens in this regard (8). Antibiotic treatment of S. aureus infections can be complicated by the prevalence of methicillin-resistant S. aureus (MRSA) strains in hospitals and increasingly in community settings (9, 10). Patients often require multiple antibiotics or use of broad-spectrum antibiotics to eradicate infection (11). Despite numerous measures taken to ensure sterility and limit spread of MRSA from health care workers to patients in hospitals (12, 13), the rate of infection remains high (14,15). While significant effort is generally focused on enforcing aseptic technique as a method to prevent infection, there may be additional factors that influence the frequency and/or severity of nosocomial infections (16).Propofol is one of the most common anesthetic agents used in the induction and maintenance of anesthesia prior to surgery, both in the intensive care unit (ICU) and in routine outpatient procedures (17)(18)(19)(20). This is in part due to its low incidence of anesthesia-related side effects and the shor...

show abstract

“…Innate myeloid cells, such as neutrophils and macrophages, play an essential role in the clearance of S. aureus (126,127). This extracellular bacterium was unexpectedly shown to induce type I IFN production.…”

Section: Staphylococcusmentioning

confidence: 99%

Interfering with Immunity: Detrimental Role of Type I IFNs during Infection

Stifter¹,

Feng²

2015

The Journal of Immunology

View full text Add to dashboard Cite

Type I IFNs are known to inhibit viral replication and mediate protection against viral infection. However, recent studies revealed that these cytokines play a broader and more fundamental role in host responses to infections beyond their well-established antiviral function. Type I IFN induction, often associated with microbial evasion mechanisms unique to virulent microorganisms, is now shown to increase host susceptibility to a diverse range of pathogens, including some viruses. This article presents an overview of the role of type I IFNs in infections with bacterial, fungal, parasitic, and viral pathogens and discusses the key mechanisms mediating the regulatory function of type I IFNs in pathogen clearance and tissue inflammation.

show abstract

Neutrophils in innate host defense against Staphylococcus aureus infections

Cited by 337 publications

References 293 publications

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

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

Propofol Sedation Exacerbates Kidney Pathology and Dissemination of Bacteria during Staphylococcus aureus Bloodstream Infections

Interfering with Immunity: Detrimental Role of Type I IFNs during Infection

Contact Info

Product

Resources

About