TY - JOUR
T1 - Neutrophil Depletion Causes a Fatal Defect in Murine Pulmonary Staphylococcus aureus clearance
AU - Robertson, Charles M.
AU - Perrone, Erin E.
AU - McConnell, Kevin W.
AU - Dunne, W. Michael
AU - Boody, Barrett
AU - Brahmbhatt, Tejal
AU - Diacovo, M. Julia
AU - Van Rooijen, Nico
AU - Hogue, Lisa A.
AU - Cannon, Carolyn L.
AU - Buchman, Timothy G.
AU - Hotchkiss, Richard S.
AU - Coopersmith, Craig M.
N1 - Funding Information:
This work was supported by funding from the National Institutes of Health (GM066202, GM072808, GM008795, GM044118, GM055194) and the Alan A. and Edith L. Wolff Foundation.
PY - 2008/12
Y1 - 2008/12
N2 - 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. Materials and methods: We examined the pathogenicity of four different strains of S. aureus (both methicillin-sensitive and -resistant as well as Panton-Valentine leukocidin-positive and -negative) in four strains of immunocompetent inbred and outbred mice (FVB/N, C57Bl/6, BALB/c, ND4; n = 148). The immunological basis for the development of murine S. aureus pneumonia was then determined by selectively depleting neutrophils, lymphocytes, or pulmonary macrophages prior to the onset of infection. An additional cohort of animals was rendered immunosuppressed by induction of abdominal sepsis via cecal ligation and puncture 2, 4, or 7 d prior to the onset of pneumonia. Results: Nearly all immunocompetent mice survived, regardless of which strain of S. aureus was used or which strain of mouse was infected. Among animals with immune depletion or prior immunosuppression, survival was decreased only following neutrophil depletion (26% versus 90% alive at 7 d, P < 0.0001). Compared to immunocompetent animals, neutrophil-depleted mice with S. aureus pneumonia had delayed pulmonary bacterial clearance at 16 and 40 h but had no difference in levels of bacteremia. Neutrophil-depleted mice also had elevated levels of pulmonary monocyte chemotactic protein-1 (822 pg/mL versus 150 pg/mL, P < 0.05). In contrast, pulmonary histological appearance was similar in both groups as was dry/wet lung weight. Conclusions: These results suggest that neutrophils play a critical role in the host response to S. aureus pneumonia, and the survival differences observed in neutrophil-depleted mice are associated with alterations in bacterial clearance and pulmonary cytokine response.
AB - 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. Materials and methods: We examined the pathogenicity of four different strains of S. aureus (both methicillin-sensitive and -resistant as well as Panton-Valentine leukocidin-positive and -negative) in four strains of immunocompetent inbred and outbred mice (FVB/N, C57Bl/6, BALB/c, ND4; n = 148). The immunological basis for the development of murine S. aureus pneumonia was then determined by selectively depleting neutrophils, lymphocytes, or pulmonary macrophages prior to the onset of infection. An additional cohort of animals was rendered immunosuppressed by induction of abdominal sepsis via cecal ligation and puncture 2, 4, or 7 d prior to the onset of pneumonia. Results: Nearly all immunocompetent mice survived, regardless of which strain of S. aureus was used or which strain of mouse was infected. Among animals with immune depletion or prior immunosuppression, survival was decreased only following neutrophil depletion (26% versus 90% alive at 7 d, P < 0.0001). Compared to immunocompetent animals, neutrophil-depleted mice with S. aureus pneumonia had delayed pulmonary bacterial clearance at 16 and 40 h but had no difference in levels of bacteremia. Neutrophil-depleted mice also had elevated levels of pulmonary monocyte chemotactic protein-1 (822 pg/mL versus 150 pg/mL, P < 0.05). In contrast, pulmonary histological appearance was similar in both groups as was dry/wet lung weight. Conclusions: These results suggest that neutrophils play a critical role in the host response to S. aureus pneumonia, and the survival differences observed in neutrophil-depleted mice are associated with alterations in bacterial clearance and pulmonary cytokine response.
KW - MCP-1
KW - Staphylococcus aureus
KW - bacteria
KW - infection
KW - model
KW - murine
KW - neutrophil
KW - pneumonia
KW - sepsis
KW - survival
UR - http://www.scopus.com/inward/record.url?scp=56449129255&partnerID=8YFLogxK
U2 - 10.1016/j.jss.2008.02.009
DO - 10.1016/j.jss.2008.02.009
M3 - Article
C2 - 18621398
AN - SCOPUS:56449129255
SN - 0022-4804
VL - 150
SP - 278
EP - 285
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 2
ER -