Essential Calcium-binding Cluster of Leptospira LipL32 Protein for Inflammatory Responses through the Toll-like Receptor 2 Pathway

Abstract

Background: LipL32 induces a renal cell inflammatory response through the TLR2-signaling pathway. Results: Ca 2ϩ -binding LipL32 mutants showed attenuated TLR2-mediated inflammatory responses. Conclusion:The Ca 2ϩ -binding cluster of LipL32 is essential in regulating its interaction with TLR2 for subsequent inflammatory response induction. Significance: This investigation provides significant evidence for crucial roles of the Ca 2ϩ -binding cluster of LipL32 for pathogenesis via association with TLR2.

Undiagnosed leptospirosis cases in naïve and vaccinated dogs: Properties of a serological test based on a synthetic peptide derived from Hap1/LipL32 (residues 154–178)

“…During in vivo multiplication and invasiveness in the infected host, the non-surface-exposed Hap1/LipL32 is required at an early stage of infection for the binding of Leptospira spp to the ECM of target cells [14,26]. The "atypical polyD motif" [28] is specifically involved in binding Hap1/LipL32 to the well-conserved TLR2 during the first step of pathogen recognition [28][29][30]. This early recognition by innate immunity could thus explain the earlier production of anti-PP antibodies, compared to agglutinating antibodies, in dogs and humans [20].…”

Decrease in antithrombin III and prothrombin serum levels contribute to coagulation disorders during leptospirosis

“…Furthermore, it has been shown that the major protein LipL32 induces inflammatory responses through the Tolllike receptor 2 pathway in human renal cells (Lo et al, 2013). .…”

Leptospiral major outer membrane protein

“…The portions responsible to bind the host lipid bilayer (noncontinuous b13-turn and C-terminal amphipathic a-6 helix), and the charged and hydrophilic amino acids were found to be important in therapeutic applications. Lo et al [28] studied the role of the calciumbinding site in the LipL32 on inflammatory response through Toll-like receptors (TLRs). Mutation-assisted studies indicated that the calcium interaction is necessary to maintain the structure of LipL32 and is a crucial factor in the interaction of LipL32 with TLR in renal cells.…”