Immunomodulatory effects of recombinant lactoferrin during MRSA infection

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) infection remains a serious hazard to global health despite increases in public education and development of innovative treatment strategies. Use of immune modulatory therapy to combat infection is gaining interest as a novel treatment alternative. Lactoferrin (LF), an iron binding protein with multiple immune modulating properties, has the potential to modify the course of systemic MRSA infection. Specifically, LF is capable of limiting deleterious inflammatory responses while promoting development of antigen specific T-cell activity. The efficacy of a novel recombinant mouse LF (rmLF) to protect against MRSA infection was examined in a mouse peritonitis model. BALB/c mice were infected with a lethal dose of MRSA and treated at 2 hours post-infection with rmLF. The effects of rmLF on MRSA-infected primary monocytes and granulocytes were analyzed for inflammatory mediator production. The rmLF treated mice demonstrated only modest increase in survival by more than 24hrs, albeit with reduced bacteremia. Serum cytokines, IL-17 and IL-6, were significantly reduced post challenge in the rmLF treated mice. Treatment with rmLF led to a minor decrease in IL-1β, and a slight increase in TNF-α production. Preliminary investigation towards human clinical relevance was accomplished using human blood derived monocytes and granulocytes infected with MRSA and treated with a homologous recombinant human LF (rhLF). Treatment with (rhLF) led to increased production of IFN-γ and IL-2. The human cell studies also showed a concurrent decrease in TNF-α, IL-6, IL-1β, IL-12p40, and IL-10. The study reports the first investigation into the efficacy of a novel recombinant mouse lactoferrin (LF) therapy in a mouse model of MRSA peritonitis. Overall, these results indicate the rmLF and rhLF have a high degree of overlap to modify inflammatory responses, although differences in activities were observed indicating existence of mechanisms between the two heterologous recombinant molecules.

Bovine lactoferrin free of lipopolysaccharide can induce a proinflammatory response of macrophages

“…LF has the potential to modify the course of an infection [42]. Being immunomodulator, LF is used as adjunct therapeutic which can alter the immune status of the infected host.…”

“…But the two heterologous recombinant molecules showed some differences in their activities concerning cellular population that were used in the studies-mouse granulocytes demonstrated a different cytokine pattern upon the infection than human granulocytes. LFs were produced under endotoxin free serum conditions, and further affinity purified to remove traces of endotoxin [42]. The data show that endotoxin-free LF has not only immunomodulatory effects but also the therapeutic effects which have different essence than just LPS binding.…”

Antibacterial Activity and Pharmacokinetic Profile of a Promising Antibacterial Agent: 22-(2-Amino-phenylsulfanyl)-22-Deoxypleuromutilin

“…Proper inflammatory response is essential to eradicate infectious microorganisms [35]. However, excessive inflammation could cause damage to the body with a large number of activated immune cells and the excessive release of inflammatory factors [36,37]. At three days after treatment, amphenmulin could significantly decreased TNF-α, IL-6, and MCP-1 in the serum in comparison to those of the infection group, avoiding the adverse effects of excessive inflammatory factors on wound healing.…”

The Iron age of host–microbe interactions

“…Activated Mø express and release lactoferrin, which scavenges and restricts Fe availability to extracellular pathogens (Fig ). Lactoferrin also protects Mø from oxidative stress and modulates Mø microbicidal activity, as shown in the context of Staphylococcus aureus infection . The Fe‐binding capacity of lactoferrin can also interfere with microbial virulence pathways such as biofilm formation .…”