Lack of association between TLR4 polymorphism and severe gram-negative bacterial infection in neonates

Abstract

Aim: Gram-negative microorganisms are responsible for a significant percentage of systemic bacterial infections in neonates, which tend to progress to sepsis. Toll-like receptor 4 (TLR4), one of the receptors in the innate immune system, binds to the lipopolysaccharide (LPS) present on gram-negative bacteria. Following ligation, a cascade of cellular signals leads to activation of NF\kappaB, resulting in the generation of such proinflammatory cytokines as TNF\alpha, IL-1, IL-2, and IL-6. These are the mediators of inflammation, which is the cellular response to activation of the innate immune system. As such, TLR4 appears to be a very likely candidate involved in the immediate immune response to gram-negative bacteria. Two polymorphisms in the TLR4 gene, Asp299Gly and Thr399Ile, cause a reduction in inflammatory cytokine response to LPS. We sought to determine if there was any correlation between these polymorphisms and severe gram-negative infection in neonates. Materials and Methods: The study included 17 neonates with severe gram-negative infection and 70 healthy controls. Results: No polymorphism was noted in the patient group. In all, 4 Asp299Gly and 7 Thr399Ile heterozygous polymorphisms were observed in the control group, and 4 subjects had both polymorphisms. Conclusion: There appeared to be no correlation between the 2 polymorphisms-Asp299Gly and Thr399Ile- and gram-negative infection.