Neutrophil depletion causes a fatal defect in murine pulmonary Staphylococcus aureus clearance.
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.


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.
Robertson
Charles M
CM
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Perrone
Erin E
EE
McConnell
Kevin W
KW
Dunne
W Michael
WM
Boody
Barrett
B
Brahmbhatt
Tejal
T
Diacovo
M Julia
MJ
Van Rooijen
Nico
N
Hogue
Lisa A
LA
Cannon
Carolyn L
CL
Buchman
Timothy G
TG
Hotchkiss
Richard S
RS
Coopersmith
Craig M
CM
D000818:Animals; D008214:Lymphocytes / Q000502:physiology; D016676:Macrophages, Alveolar / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology*; D011023:Pneumonia, Staphylococcal / Q000150:complications / Q000276:immunology*; D018805:Sepsis / Q000150:complications; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity