Combined Stimulation of Toll-Like Receptor 5 and NOD1 Strongly Potentiates Activity of NF-κB, Resulting in Enhanced Innate Immune Reactions and Resistance to Salmonella enterica Serovar Typhimurium Infection

• DOI: 10.1128/iai.00525-13
• Publication Date: 2013-07-30T03:01:12Z
• Authors: Amir I. Tukhvatulin; Ilya I. Gitlin; Dmitry V. Shchebl...; Natalia M. Artemi...; Lyudmila G. Burdelya; Maxim M. Shmarov; Boris S. Naroditsky; Andrei V. Gudkov; Alexander L. Gint...; Denis Y. Logunov
• Keywords: NOD1; TLR5; Salmonella enterica

Pathogen recognition receptors (PRRs) are essential components of host innate immune systems that detect specific conserved pathogen-associated molecular patterns (PAMPs) presented by microorganisms. Members two families PRRs, transmembrane Toll-like (TLRs 1, 2, 4, 5, and 6) cytosolic NOD (NOD1 NOD2), stimulated upon various bacterial PAMPs. Such stimulation leads to induction a number defense reactions, mainly triggered via activation the transcription factor NF-κB. While coordination responses initiated different PRRs sensing multiple PAMPS present during an infection makes clear biological sense for host, such interactions have not been fully characterized. Here, we demonstrate combined NOD1 TLR5 (as well as other TLR family members) strongly potentiates activity NF-κB induces enhanced levels reactions (e.g., cytokine production) both in vitro vivo. Moreover, show increased level plays critical role formation downstream responses. In live mice, synergy between these resulting potentiation was organ specific, being most prominent gastrointestinal tract. Coordinated significantly protection mice against enteroinvasive Salmonella infection. Obtained results suggest cooperation is important effective microbial