Weil's Disease-Immunopathogenesis, Multiple Organ Failure, and Potential Role of Gut Microbiota

Abstract

Leptospirosis is an important zoonotic disease, causing about 60,000 deaths annually. In this review, we have described in detail the immunopathogenesis of leptospirosis, the influence of cytokines, genetic susceptibility on the course of the disease, and the evasion of the immune response. These data are combined with information about immunological and pathomorphological changes in the kidneys, liver, and lungs, which are most affected by Weil's disease. The review also suggests a possible role of the gut microbiota in the clinical course of leptospirosis, the main mechanisms of the influence of gut dysbiosis on damage in the liver, kidneys, and lungs through several axes, i.e., gut-liver, gut-kidney, and gut-lungs. Modulation of gut microbiota by probiotics and/or fecal microbiota transplantation in leptospirosis may become an important area of scientific research.

Keywords: Weil’s disease; dysbiosis; leptospirosis.

Figure 1

Schematic representation of the architecture of the leptospiral membrane. The inner membrane is closely associated with the peptidoglycan cell wall, which is overlaid by the outer membrane. Surface-exposed lipoproteins (LipL32, LigA, LigB), the transmembrane outer membrane protein porin L1 (OmpL1), and lipopolysaccharide are among the main components of the outer membrane.

Figure 2

Key links in the immunopathogenesis of leptospirosis: (a) recruitment of neutrophils to the inflammatory zone and formation of NETs; (b) activation of differentiation of pro-inflammatory subpopulations of T-helpers; (c) increase in pro-inflammatory signaling against the background of deficiency of suppressor signals and Treg cells; (d) activation of M1-macrophages, stimulation of TLR2; (e) NLR with subsequent formation of NLRP3-inflammasome and subsequent maturation of IL1b; (f) -formation of MAC and destruction of the cell membrane.

Figure 3

Pathogenesis of hemorrhagic syndrome in human leptospirosis.

Figure 4

Commensal bacteria can influence the induction of intestinal T-helper cells in Gut-associated lymphoid tissue. Altered intestinal T helper cell profiles can have pathological consequences that are not limited to intestinal sites.

Figure 5

The influence of altered gut microbiota on the course of leptospirosis. According to our hypothesis, leptospirosis-induced gut dysbiosis can lead to a pro-inflammatory immune response, which can be one of the factors that lead to a severe course of leptospirosis.