Bacteremia in Intensive Care Unit (ICU) and the Role of Toll-Like-Receptors (TLRs)

INTRODUCTION Bacteremia is associated with significant morbidity and mortality in critically ill patients and increased the length of hospitalization. Incidence of bacteremia in Intensive Care Units ranges from 8 to 10% and mortality 40%.

Risk factors for the development of bacteremia include the presence of central intravascular catheters, hemodialysis, the use of parenteral nutrition, urine catheters, endotracheal tubes, mechanical ventilation, underlying diseases like cancer, various immunocompromised states, mellitus diabetes, malnutrition, renal and liver failure, transplantations, surgery operations, burns.

The most common microbial pathogens which cause bacteremia are Gram negative pathogens, Pseudomonas species, Staphylococcus aureus, Klebsiella species, Pseudomonas aeruginosa, Candida albicans, Acinetobacter baumanii, Streptococcus pneumoniae.

Toll-like receptors (TLRs) are important for the activation of innate immunity against microbial pathogens. TLRs are transmembrane proteins and are composed of leukine rich extracellular domain, a short intramembrane segment and an intracytoplasmic domain. Intracytoplasmic domain is similar to that of interleukin-1 (IL-1) receptor.

In humans, they have been identified eleven types of recognizing specific pathogen-associated molecular patterns (PAMPs). TLR1 and TLR2 form a heterodimer recognizing bacterial tri-acylated lipopeptides of Gram-positive bacteria. TLR2 and TLR6 form another heterodimer recognizing di-acylated lipopeptides of Gram-positive bacteria. TLR4 is a heterodimer recognizing lipopolysacharedes (LPS)of Gram-negative bacteria while TLR5 is a receptor recognizing flagellae of Gram-negative bacteria. All these aforementioned types of TLRs are expressed on the outer surface of the cell membrane. TLR3, TLR7 TRL8 and TLR9 is a group of receptors expressed on an internal surface of the phagosomes formed in the cytoplasm after the ingestion of the pathogens.TLR3 recognizes viral dsRNA, TLR7 recognizes imidazol-quinollines, TLR8 recognize ssRNA and TLR9 recognize non-methylated bacterial CpG DNA. In addition to bacterial and viral CpG DNA, TLR9 is presumably involved in pathogenesis of autoimmune disorders. TLR10 and TLR11 are still under investigation, although TLR11 seem to recognize uropathogenic bacteria.