Abstract
BackgroundLeptospirosis is caused by pathogenic spirochetes of the genus Leptospira. The bacteria enter the human body via abraded skin or mucous membranes and may disseminate throughout. In general the clinical picture is mild but some patients develop rapidly progressive, severe disease with a high case fatality rate. Not much is known about the innate immune response to leptospires during haematogenous dissemination. Previous work showed that a human THP-1 cell line recognized heat-killed leptospires and leptospiral LPS through TLR2 instead of TLR4. The LPS of virulent leptospires displayed a lower potency to trigger TNF production by THP-1 cells compared to LPS of non-virulent leptospires.Methodology/Principal FindingsWe investigated the host response and killing of virulent and non-virulent Leptospira of different serovars by human THP-1 cells, human PBMC's and human whole blood. Virulence of each leptospiral strain was tested in a well accepted standard guinea pig model. Virulent leptospires displayed complement resistance in human serum and whole blood while in-vitro attenuated non-virulent leptospires were rapidly killed in a complement dependent manner. In vitro stimulation of THP-1 and PBMC's with heat-killed and living leptospires showed differential serovar and cell type dependence of cytokine induction. However, at low, physiological, leptospiral dose, living virulent complement resistant strains were consistently more potent in whole blood stimulations than the corresponding non-virulent complement sensitive strains. At higher dose living virulent and non-virulent leptospires were equipotent in whole blood. Inhibition of different TLRs indicated that both TLR2 and TLR4 as well as TLR5 play a role in the whole blood cytokine response to living leptospires.Conclusions/SignificanceThus, in a minimally altered system as human whole blood, highly virulent Leptospira are potent inducers of the cytokine response.
Highlights
Leptospirosis transmission occurs worldwide and comprises all infections caused by pathogenic spirochetes of the genus Leptospira [1]
The virulence of the L. interrogans strains used of serovars Bataviae and Lai was evaluated in the standard guinea pig model by i.p. injection of viable bacteria
The disease is caused by strains of the Leptospira bacteria that may differ in their LPS moiety which is used to discriminate the different leptospiral serovars [3]
Summary
Leptospirosis transmission occurs worldwide and comprises all infections caused by pathogenic spirochetes of the genus Leptospira [1]. Being spread by the urine of infected animals, the bacteria enter the human body via abraded skin, conjunctivae or mucous membranes, after which they may disseminate throughout the body. Some patients develop severe disease, which is often rapidly progressive and can be fatal in up to 70% of patients with severe pulmonary disorders [3]. The clinical picture of severe leptospirosis is dominated by hepato-renal impairment and hemorrhages. Leptospirosis is caused by pathogenic spirochetes of the genus Leptospira. The bacteria enter the human body via abraded skin or mucous membranes and may disseminate throughout. In general the clinical picture is mild but some patients develop rapidly progressive, severe disease with a high case fatality rate. The LPS of virulent leptospires displayed a lower potency to trigger TNF production by THP-1 cells compared to LPS of non-virulent leptospires
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
