Deficiency of Mannose-Binding Lectin Greatly Increases Susceptibility to Postburn Infection withPseudomonas aeruginosa

Abstract

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.

Mannose-Binding Lectin A-Deficient Mice Have Abrogated Antigen-Specific IgM Responses and Increased Susceptibility to a Nematode Infection

“…Staphylococcus aureus infection (5). MBL null mice are also more susceptible to postburn infection with Pseudomonas aeruginosa (12). However, in these studies, loss of both MBL-A and MBL-C is needed for the increased susceptibility, and it has yet to be determined whether MBL-A and MBL-C can differ in their pathogen specificity.…”

“…However, splenic dendritic cells and peritoneal macrophages taken from MBL-A and C Ϫ/Ϫ mice express similar amounts of costimulatory molecules and MHC to WT mice (21). Thus, in different contexts, MBL has been shown to induce or modulate proinflammatory responses, and it has yet to be definitively determined whether MBL performs different roles depending on whether it recognizes carbohydrates on the pathogen surface or it recognizes altered self in the context of necrotic and apoptotic cells (12).…”

Synergistic regulation of Pseudomonas aeruginosa‐induced cytokine production in human monocytes by mannose receptor and TLR2

“…Binding of mannose to lectin prevents systemic spread of local inflammation in patients suffering from P. aeruginosa infections after burn [54]. Alternatively, down-regulation of MR expression in alveolar macrophages of HIV-infected patients correlates with increased susceptibility to opportunistic pathogens [44,55].…”

Influence of mannose-binding lectin genotypes and serostatus in allo-SCT: analysis of 131 recipients and donors

“…In ex vivo experiments, MBL levels had a dose-dependent effect on the inflammatory response to Neisseria meningitides, 26 and MBL influenced anti-inflammatory cytokines. 27 The balance between pro-and anti-inflammatory responses has been shown to influence the susceptibility to sepsis; 28 therefore high and low MBL levels might increase sepsis rates. High MBL levels may also merely reflect the inflammatory response to infection.…”