Adipose tissue is the first colonization site of Leptospira interrogans in subcutaneously infected hamsters

Abstract

Leptospirosis is one of the most widespread zoonoses in the world, and its most severe form in humans, “Weil’s disease,” may lead to jaundice, hemorrhage, renal failure, pulmonary hemorrhage syndrome, and sometimes,fatal multiple organ failure. Although the mechanisms underlying jaundice in leptospirosis have been gradually unraveled, the pathophysiology and distribution of leptospires during the early stage of infection are not well understood. Therefore, we investigated the hamster leptospirosis model, which is the accepted animal model of human Weil’s disease, by using an in vivo imaging system to observe the whole bodies of animals infected with Leptospira interrogans and to identify the colonization and growth sites of the leptospires during the early phase of infection. Hamsters, infected subcutaneously with 104 bioluminescent leptospires, were analyzed by in vivo imaging, organ culture, and microscopy. The results showed that the luminescence from the leptospires spread through each hamster’s body sequentially. The luminescence was first detected at the injection site only, and finally spread to the central abdomen, in the liver area. Additionally, the luminescence observed in the adipose tissue was the earliest detectable compared with the other organs, indicating that the leptospires colonized the adipose tissue at the early stage of leptospirosis. Adipose tissue cultures of the leptospires became positive earlier than the blood cultures. Microscopic analysis revealed that the leptospires colonized the inner walls of the blood vessels in the adipose tissue. In conclusion, this is the first study to report that adipose tissue is an important colonization site for leptospires, as demonstrated by microscopy and culture analyses of adipose tissue in the hamster model of Weil’s disease.

Recent findings related to immune responses against leptospirosis and novel strategies to prevent infection

“…Recently, the Yoshida group used a hamster model of intradermal inoculation to track post-mortem, after laparotomy, the Murray's LuxCDABE-luminescent L. interrogans. Of great interest, they showed that leptospires first disseminate in the subcutaneous adipose tissue before disseminating in the blood and colonizing the organs including the kidneys [45]. Eye drop inoculation is an interesting route of infection since it mimics a natural route of infection and is considered more physiological than intraperitoneal infection, which bypasses the natural defenses of the skin and mucosa.…”

An extracellular Leptospira interrogans leucine‐rich repeat protein binds human E‐ and VE‐cadherins

“…Furthermore, pathogenic, but not saprophytic, Leptospira have been shown to interrupt cell-to-cell junctions in vitro (Sato & Coburn, 2017). Enhanced vascular permeability facilitated by LIC10831 may allow the bacterium to escape host blood vessels to take up residence in preferred host tissues (Barnett et al, 1999;Ozuru et al, 2017).…”

Identification of a cis-acting determinant limiting expression of sphingomyelinase genesph2inLeptospira interroganswith agfpreporter plasmid

“…In each of these cases, 69 regulation of pathogenic gene expression was examined in a surrogate host because a plasmid 70 able to replicate in L. interrogans was not available. Promoter fusions to gfp or luciferase genes 71 have been introduced into L interrogans by transposition (21)(22)(23). However, mutational analysis 72 of promoters fused to the reporter is not possible with the transposon-based system; random 73 insertion of the transposon carrying the fusion complicates interpretation of expression levels 74 because the location of the transposon in the chromosome may influence fusion expression.…”