Survival of Staphylococcus aureus inside neutrophils contributes to infection.
Neutrophils have long been regarded as essential for host defense against Staphylococcus aureus infection. However, survival of the pathogen inside various cells, including phagocytes, has been proposed as a mechanism for persistence of this microorganism in certain infections. Therefore, we investigated whether survival of the pathogen inside polymorphonuclear neutrophils (PMN) contributes to the pathogenesis of S. aureus infection. Our data demonstrate that PMN isolated from the site of infection contain viable intracellular organisms and that these infected PMN are sufficient to establish infection in a naive animal. In addition, we show that limiting, but not ablating, PMN migration into the site of infection enhances host defense and that repletion of PMN, as well as promoting PMN influx by CXC chemokine administration, leads to decreased survival of the mice and an increased bacterial burden. Moreover, a global regulator mutant of S. aureus (sar-) that lacks the expression of several virulence factors is less able to survive and/or avoid clearance in the presence of PMN. These data suggest that the ability of S. aureus to exploit the inflammatory response of the host by surviving inside PMN is a virulence mechanism for this pathogen and that modulation of the inflammatory response is sufficient to significantly alter morbidity and mortality induced by S. aureus infection.
Gresham
H D
HD
Research Service, Albuquerque Veterans Affairs Medical Center, Albuquerque, NM, 87108, USA. hgersham@salud.unm.edu
Lowrance
J H
JH
Caver
T E
TE
Wilson
B S
BS
Cheung
A L
AL
Lindberg
F P
FP
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000235:genetics; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D054426:Chemokine CXCL2; D018925:Chemokines / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D007424:Intracellular Fluid / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology / Q000648:ultrastructure; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology* / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000254:growth & development* / Q000276:immunology* / Q000472:pathogenicity / Q000648:ultrastructure; D015534:Trans-Activators; D014617:Vacuoles / Q000276:immunology / Q000382:microbiology / Q000648:ultrastructure
D015703:Antigens, CD; D001426:Bacterial Proteins; D051928:CD47 Antigen; D002352:Carrier Proteins; C497895:Cd47 protein, mouse; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; C088021:SarA protein, bacterial; D015534:Trans-Activators