Tubulointerstitial nephritis is a cardinal renal manifestation in leptospirosis and LipL32, the major lipoprotein component of leptospiral outer membrane proteins (OMPs), induces a robust inflammatory response in cultured renal proximal tubule cells through a nuclear factor-kappaB-related pathway. Here, we investigated whether Toll-like receptor (TLR), known to play a pivotal role in innate immunity, could mediate the inflammatory response induced by leptospiral OMPs in renal proximal tubule cells. TLR expression was analyzed by flow cytometry and indirect immunofluorescence in cultured mouse proximal tubule (pyruvate kinase simian virus 40-proximal straight (PKSV-PR)) cells. Reverse transcription-competitive polymerase chain reaction and enzyme-linked immunosorbent assay were undertaken to analyze the inducible effects of inducible nitric oxide synthase (iNOS) and monocyte chemoattractant protein-1 (MCP-1 also termed CCL2) by pathogenic and non-pathogenic leptospiral OMPs and recombinant lipoproteins in either PKSV-PR cells or TLR-transfected human embryonic kidney (HEK) 293 cells. Anti-TLR antibodies were used for blocking experiments. Leptospira santarosai serovar Shermani OMPs and LipL32 induced a significant increase in TLR2 but not TLR4 expression in PKSV-PR cells. The increase in iNOS and CCL2/MCP-1 mRNA expressions could be prevented by an anti-TLR2 antibody, but not by an anti-TLR4 antibody. Furthermore, leptospiral OMPs stimulated both CCL2/MCP-1 mRNA and secreted protein in transfected HEK 293 cells with a TLR2-expressing plasmid, but had no effect in cells with a TLR4-expressing plasmid. In conclusion, these findings indicate that the stimulation of iNOS and CCL2/MCP-1 caused by pathogenic leptospiral OMPs, in particular LipL32, in proximal tubule cells requires TLR2 for the early inflammatory response.

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Only a few studies have investigated the use of PCT in the diagnosis of bone and joint infection, and these studies have had relatively small sample sizes. We performed a systematic review and meta-analysis of the diagnostic performance of serum procalcitonin (PCT) in the identification of osteomyelitis and septic arthritis in patients who present with fever and orthopedic symptoms. EMBASE, MEDLINE, and Cochrane databases and the reference lists of relevant articles were searched, with no language restrictions, through February 2012. All original studies that reported the use of serum PCT alone or in comparison with other biomarkers for diagnosis of osteomyelitis and septic arthritis were included. Seven studies qualified for inclusion. These studies enrolled a total of 583 patients with suspected bone or joint infection, 131 of whom had confirmed osteomyelitis or septic arthritis. Analysis of the PCT data indicated a bivariate pooled sensitivity of 0.67 (95 % CI: 0.37-0.88), specificity of 0.90 (95 % CI: 0.78-0.96), a positive likelihood ratio (LR+) of 6.48 (95 % CI: 2.28-14.6), and a negative likelihood ratio (LR-) of 0.37 (95 % CI: 0.16-0.84). Use of a lower PCT cut-off value (0.2-0.3 ng/mL) improved the LR + to 6.66 and the LR- to 0.15. Analysis of the three studies that also measured serum C-reactive protein (CRP) indicated that CRP had an LR + of 1.39 (95 % CI: 1.17-1.65) and an LR- of 0.40 (95 % CI: 0.12-1.36). Our results indicate that PCT may be more suitable as an aid for rule-in diagnosis rather than for exclusion of septic arthritis or osteomyelitis and that use of a lower cut-off value for serum PCT may improve its diagnostic performance.