Leptospirosis Antibodies, Proteins & ELISA Kits

Leptospirosis (Weil's disease) is caused by zoonotic gram-negative spirochete bacterial pathogens belonging to the Leptospira species. The main modes of transmission are either through direct contact with animals infected with Leptospirosis or through indirect contact with contaminated water or soil with urine from infected animals.

Leptospirosis is endemic in many tropical regions such as South America and Asia. Leptospira species can infect a wide range of animals but the main reservoir host is Rattus norvegicus, commonly known as the brown rat. There is a high antigenic similarity between Leptospira species and because of this they are divided into different serovars.

According to the World Health Organization (WHO), there is an estimation of 873,000 leptospirosis cases annually with up to 40,000 of them resulting in mortality. The symptoms of leptospirosis range from fever, jaundice and vomiting to diarrhea and multiorgan failure. There is a leptospirosis vaccine available for human use in China and Cuba presently, however, there is a need for further research to understand the pathogenesis of Leptospira in order to improve both current and emerging vaccines.

It is important to know what host receptors bind to Leptospira species during leptospirosis infections in order to properly understand the effect that the bacteria has on the body while an immune response is elicited. DC-specific intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN) receptor on dendritic cells are able to bind to L.interrogans serovars in order to produce cytokines such as IL-12p70 and TNF-alpha.

As well as this, toll-like receptors (TLRs) are involved in recognizing Leptospira species. There have been numerous studies which have examined the TLR response during leptospirosis infections and it was discovered that TLR4 only recognizes lipopolysaccharide (LPS) of Leptospira in mice and not in humans. However, TLR2 is capable of recognizing LPS of Leptospira in both mice and humans.

Reactive oxygen species (ROS) are produced by macrophages from mice and they have a bactericidal ability to kill intracellular leptospires. However, ROS does not contribute as much in human macrophage elimination of leptospires and this may account for the fact that there is a difference between the intracellular fates of L. interrogans in mice and humans. There is also the induction of nitric oxide synthase (iNOS) in hosts when pro-inflammatory cytokines such as IL-6 and TNF-alpha are produced. The iNOS then produces nitric oxide (NO) which has bacteriostatic effects. In a previous study an iNOS inhibitor called 4-aminopyridine (4-AP) was used to treat Golden Syrian hamsters with leptospirosis The results were that there was an acceleration of mortality rate and there was an increased bacterial burden in the kidneys. This highlights the important role which NO has in fighting leptospirosis infections.

A key area of research is the immune response to leptospirosis infections. It is believed that the organ damage which is observed in leptospirosis is caused by the immune response to Leptospira bacteria. Once the host immune system detects pathogen-associated molecular patterns (PAMPs) of Leptospira there is the production of cytokines and chemokines such as interleukin-6 (IL-6), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), IL-10, IL-8, IL-12p70, interferon-gamma (IFN-gamma), monocyte chemoattractant protein-1 (CCL2), cathelicidin peptide LL-37, CXCL10 (IP-10) and CXCL9. There is also the production of host pentraxins (PTX3) which function as opsonins and can regulate aspects of the complement system. In sheep and cattle studies cathelicidin peptide LL-37 is capable of killing L.interrogans but in humans it has reduced activity.

Studies have shown that upon interaction with macrophages, Leptospira species downregulates a number of genes involved in metabolism such as oxidative phosphorylation and the citric acid (TCA) cycle. Instead, Leptospira utilizes fatty acid oxidation (FAO) in order to generate energy. Examining the metabolic pathways which Leptospira uses during disease pathogenesis could be a possible avenue to investigate in order to see if alterations in pathogen metabolism could be linked to immune evasion strategies and how infections persist in the body during leptospirosis.

Another area of interest during vaccine development is immunometabolism, which encompasses aspects of both immunology and metabolism. Many of the functional capacities of immune cells are dependent on the metabolic state of the cell and its capability to mount an immune response. At present, there is very little research covering how immune cell metabolism is affected by Leptospira infection and this could be a possible research area to investigate in the future. Assay Genie provides a wide range of immunometabolism assays such as glycolysis assays, fatty acid oxidation assays and TCA cycle assays.

Animal models are useful research tools which are often used in early stages of therapeutic product development and pathogenesis studies. The Syrian hamster model is a suitable model for studying leptospirosis infections because it mirrors the disease symptoms observed in leptospirosis infected humans and it is commonly used for potency testing of vaccines.

It has also been shown that mice are not susceptible to leptospirosis but both transgenic and mutant murine models have been used to study the pathogenesis of leptospirosis. Lethal forms of leptospirosis have been observed in mice studies consisting of C3H/HeJ mice who are TLR4 deficient and C57BL/6 mice who are both TLR2 and TLR4 deficient. It is also known that some mice are resistant to Leptospira infection, such as Oncins France 1 (OF1) mice. The immune response elicited against Leptospira in hamster models has been compared to OF1 mice in many studies in order to decipher the major differences which characterize susceptible animals from resistant animals.