Deficiency of mannose-binding lectin greatly increases susceptibility to postburn infection with Pseudomonas aeruginosa.
Burn injury disrupts the mechanical and biological barrier that the skin presents against infection by symbionts like the Pseudomonas aeruginosa, a Gram-negative bacteria. A combination of local factors, antimicrobial peptides, and resident effector cells form the initial response to mechanical injury of the skin. This activity is followed by an inflammatory response that includes influx of phagocytes and serum factors, such as complement and mannose-binding lectin (MBL), which is a broad-spectrum pattern recognition molecule that plays a key role in innate immunity. A growing consensus from studies in humans and mice suggests that lack of MBL together with other comorbid factors predisposes the host to infection. In this study we examined whether MBL deficiency increases the risk of P. aeruginosa infection in a burned host. We found that both wild-type and MBL null mice were resistant to a 5% total body surface area burn alone or s.c. infection with P. aeruginosa alone. However, when mice were burned then inoculated s.c. with P. aeruginosa at the burn site, all MBL null mice died by 42 h from septicemia, whereas only one-third of wild-type mice succumbed (p = 0.0005). This result indicates that MBL plays a key role in containing and preventing a systemic spread of P. aeruginosa infection following burn injury and suggests that MBL deficiency in humans maybe a premorbid variable in the predisposition to infection in burn victims.
Møller-Kristensen
Mette
M
Laboratory of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Ip
W K Eddie
WK
Shi
Lei
L
Gowda
Lakshmi D
LD
Hamblin
Michael R
MR
Thiel
Steffen
S
Jensenius
Jens Chr
JC
Ezekowitz
R Alan B
RA
Takahashi
Kazue
K
D000818:Animals; D002056:Burns / Q000097:blood / Q000235:genetics / Q000382:microbiology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D037601:Mannose-Binding Lectin / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D011552:Pseudomonas Infections / Q000097:blood; D011550:Pseudomonas aeruginosa; D012307:Risk Factors; D018805:Sepsis / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D037601:Mannose-Binding Lectin; D014409:Tumor Necrosis Factor-alpha