Neutrophil Depletion Causes a Fatal Defect in Murine Pulmonary Staphylococcus aureus clearance

Robertson, Charles M.; Perrone, Erin E.; McConnell, Kevin W.; Dunne, W. Michael; Boody, Barrett; Brahmbhatt, Tejal S.; Diacovo, Maria Julia; Rooijen, Nico van; Hogue, Lisa A.; Cannon, Carolyn L.; Buchman, Timothy G.; Hotchkiss, Richard S.; Coopersmith, Craig M.

doi:10.1016/j.jss.2008.02.009

Cited by 84 publications

(78 citation statements)

References 37 publications

(24 reference statements)

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“…As a successful human pathogen, S. aureus has evolved many mechanisms to counteract neutrophils (9). While neutrophils are absolutely necessary for the eradication of staphylococcal infections (68,69), their presence during infection has also been described as pathogenic (66,70). IP-10, which we showed to be upregulated systemically by SEA, can promote phagocytosis (71); however, MIP-2, which is also upregulated, is capable of enhancing intracellular bacterial survival within neutrophils (66,70).…”

Section: Discussionmentioning

confidence: 94%

Superantigens Subvert the Neutrophil Response To Promote Abscess Formation and Enhance Staphylococcus aureus SurvivalIn Vivo

Gilmore

Szabo

et al. 2014

Infect Immun

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Section: Discussionmentioning

confidence: 94%

Superantigens Subvert the Neutrophil Response To Promote Abscess Formation and Enhance Staphylococcus aureus SurvivalIn Vivo

Gilmore

Szabo

et al. 2014

Infect Immun

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“…aureus causes an especially severe pneumonia, marked by an intense proinflammatory response that interferes with respiration and causes excessive mortality (15). While PMNs are required to effect bacterial clearance (19), accumulating data suggest that the regulation of PMN recruitment and their activation status may be critical in determining the outcome of the S. aureus infection (17,18). In our studies, significantly increased mortality was observed in clodronate-treated mice; these mice had an increased DC population, increased CXCR3 ligand expression, and increased CD4 ϩ population, as well as decreased macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…PMNs have long been thought to be critical for efficient staphylococcal clearance (19,22), and the increased incidence of severe staphylococcal infection in humans with disorders of PMN function or activation, such as chronic granulomatous disease (10, 12), confirm this observation. PMNs themselves can also contribute to the pathology associated with staphylococcal infection.…”

mentioning

confidence: 93%

Participation of CD11c ⁺ Leukocytes in Methicillin-Resistant Staphylococcus aureus Clearance from the Lung

et al. 2011

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Staphylococcus aureus causes especially severe pulmonary infection, associated with high morbidity and mortality. In addition to the effects of specific virulence factors, it appears that the intensity of the host proinflammatory response, particularly in the initial stages of infection, contributes substantially to pulmonary damage. We tested the hypothesis that the CD11c ؉ leukocytes are important in the host response to pulmonary infection with methicillin-resistant S. aureus (MRSA) USA300. Clodronate-induced depletion of the alveolar macrophage population resulted in increased numbers of dendritic cells (DCs) and CD4؉ cells in bronchoalveolar lavage (BAL) fluid and was associated with significantly increased mortality by 18 h following S. aureus inoculation but had no effect on bacterial load or polymorphonuclear leukocyte (PMN) numbers in the lung. These clodronate-treated mice also had increased expression of interleukin-17A/F (IL-17A/F) and Staphylococcus aureus bacteria, particularly the epidemic methicillin-resistant USA300 strains, have recently been associated with severe invasive pneumonias in previously well individuals, as well as being a complication of influenza (15). These pneumonias are characterized by a predominant polymorphonuclear leukocyte (PMN) response with significant areas of necrosis and hemorrhage (6). Numerous studies have addressed which of the several virulence factors expressed by the USA300 strains are most important in the pathogenesis of pulmonary infection. In the C57BL/6J mouse model of acute pneumonia, the contributions of ␣-hemolysin (Hla) (3) and protein A (SpA) (8) have been well documented. The importance of Panton-Valentine leukocidin (PVL) has also been confirmed in a rabbit model of infection; rabbits, like humans, have highly PVL-susceptible leukocytes (6). Besides the direct toxicity of staphylococcal toxins, some of the pathological consequences of staphylococcal virulence factors are due to the intensity of the host immune response. Both Tnfr1 Ϫ/Ϫ (8) and Ifnar Ϫ/Ϫ (17) mice are highly resistant to S. aureus pneumonia and even to the USA300 strains expressing these virulence factors, suggesting that the intensity of the host immune response to infection is critical in the pathogenesis of severe pneumonia.Exactly which components of the innate immune response contribute to lethality in these models of acute S. aureus pneumonia has not been clearly delineated. PMNs have long been thought to be critical for efficient staphylococcal clearance (19,22), and the increased incidence of severe staphylococcal infection in humans with disorders of PMN function or activation, such as chronic granulomatous disease (10, 12), confirm this observation. PMNs themselves can also contribute to the pathology associated with staphylococcal infection. A substantial component of the lung pathology associated with S. aureus USA300 pneumonia has been attributed to the PVL-associated release of cytotoxic components from PMN granules (5). In models of soft tissue infection, the importance ...

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“…Circulating neutrophils are recruited rapidly to infectious areas through chemotactic signals and eliminate bacteria by bactericidal and phagocytic mechanisms [2,3,26] . Depletion of neutrophils delays bacterial clearance and causes lethality in mouse lung infection [27] . Considering that neutrophils are the most professional effect or cells against foreign pathogens, the capacity of KRT to promote bactericidal functions of neutrophils should be noted.…”

Section: Ly6gmentioning

confidence: 99%

Keigairengyoto, a traditional Japanese medicine, promotes bacterial clearance by activating innate immune cells in mouse cutaneous infection models

et al. 2017

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Prompt elimination of pathogens including bacteria and dead cells prevents the expansion of secondary and prolonged inflammations and tissue damage. Keigairengyoto (KRT) is a traditional Japanese medicine prescribed for dermatoses such as purulent inflammations. Our aim is to clarify the actions of KRT in bacterial clearance and to examine the cell-kinetic profiles of phagocytes. In a mouse cutaneous infection model using living Staphylococcus aureus, KRT drastically reduced the number of bacteria in the infection sites. To evaluate the bacterial clearance, pseudo-infection was induced in mouse ears by intradermal injection of FITC-conjugated dead S. aureus. Biochemical and histological examinations revealed that KRT promoted bacterial clearance at 6 and 24 h post-injection. The numbers and phagocytic activities of neutrophils and macrophages in the ears were evaluated histologically using anti-Ly6G and F4/80 antibodies. KRT reduced bacterial deposition and increased the accumulation of F4/80 + resident macrophages around the lesion site. FACS analysis was performed on single cell suspensions dispersed enzymatically from skin lesions, followed by an investigation of CD11b + Ly6G + (neutrophils) and CD11b + Ly6G -(monocytes/macrophages) cells. KRT increased the mean fluorescent intensity of FITC in CD11b Ly6G-cells and the number of FITCpositive CD11b + Ly6G+ cells, while KRT did not change the numbers of these cells. To investigate the active constituents of KRT, phagocytosis assay using macrophages was performed, resulting in that some flavonoid glucuronides of KRT derivatives augmented phagocytosis. Collectively, KRT promoted bacterial clearance by enhancing the phagocytic capability of neutrophils and macrophages. KRT may exert unique properties in preventive and therapeutic strategies for skin infectious inflammation.

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Neutrophil Depletion Causes a Fatal Defect in Murine Pulmonary Staphylococcus aureus clearance

Abstract: Background-Staphylococcus aureus is the most common cause of healthcare-associated pneumonia. Despite the significant morbidity and mortality associated with the disease, animal models of S. aureus pneumonia are rare.

Cited by 84 publications

References 37 publications

Superantigens Subvert the Neutrophil Response To Promote Abscess Formation and Enhance Staphylococcus aureus SurvivalIn Vivo

Superantigens Subvert the Neutrophil Response To Promote Abscess Formation and Enhance Staphylococcus aureus SurvivalIn Vivo

Participation of CD11c ⁺ Leukocytes in Methicillin-Resistant Staphylococcus aureus Clearance from the Lung

Keigairengyoto, a traditional Japanese medicine, promotes bacterial clearance by activating innate immune cells in mouse cutaneous infection models

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Neutrophil Depletion Causes a Fatal Defect in Murine Pulmonary Staphylococcus aureus clearance

Abstract: Background-Staphylococcus aureus is the most common cause of healthcare-associated pneumonia. Despite the significant morbidity and mortality associated with the disease, animal models of S. aureus pneumonia are rare.

Cited by 84 publications

References 37 publications

Superantigens Subvert the Neutrophil Response To Promote Abscess Formation and Enhance Staphylococcus aureus SurvivalIn Vivo

Superantigens Subvert the Neutrophil Response To Promote Abscess Formation and Enhance Staphylococcus aureus SurvivalIn Vivo

Participation of CD11c + Leukocytes in Methicillin-Resistant Staphylococcus aureus Clearance from the Lung

Keigairengyoto, a traditional Japanese medicine, promotes bacterial clearance by activating innate immune cells in mouse cutaneous infection models

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Participation of CD11c ⁺ Leukocytes in Methicillin-Resistant Staphylococcus aureus Clearance from the Lung