Host and Species-Specificities of Pattern Recognition Receptors Upon Infection With Leptospira interrogans

Abstract

Leptospirosis is a zoonotic infectious disease affecting all vertebrates. It is caused by species of the genus Leptospira, among which are the highly pathogenic L. interrogans. Different mammals can be either resistant or susceptible to the disease which can present a large variety of symptoms. Humans are mostly asymptomatic after infection but can have in some cases symptoms varying from a flu-like syndrome to more severe forms such as Weil’s disease, potentially leading to multiorgan failure and death. Similarly, cattle, pigs, and horses can suffer from acute forms of the disease, including morbidity, abortion, and uveitis. On the other hand, mice and rats are resistant to leptospirosis despite chronical colonization of the kidneys, excreting leptospires in urine and contributing to the transmission of the bacteria. To this date, the immune mechanisms that determine the severity of the infection and that confer susceptibility to leptospirosis remain enigmatic. To our interest, differential immune sensing of leptospires through the activation of or escape from pattern recognition receptors (PRRs) by microbe-associated molecular patterns (MAMPs) has recently been described. In this review, we will summarize these findings that suggest that in various hosts, leptospires differentially escape recognition by some Toll-like and NOD-like receptors, including TLR4, TLR5, and NOD1, although TLR2 and NLRP3 responses are conserved independently of the host. Overall, we hypothesize that these innate immune mechanisms could play a role in determining host susceptibility to leptospirosis and suggest a central, yet complex, role for TLR4.

Evolutionary insights into the emergence of virulentLeptospiraspirochetes

“…Pathogenic Leptospira , like most other pathogenic spirochetes, are stealthy pathogens that can escape the recognition by the host innate immune system [26]. We thus asked if P1- species had evolved similar strategies to escape or modulate host immunity during infection.…”

Leptospira interrogans prevents macrophage cell death and pyroptotic IL1β release through its atypical lipopolysaccharide

“…Mice are resistant to the acute form of the disease and get chronically infected in their kidneys. On the other hand, humans and bovines are susceptible and present diverse symptoms (Bonhomme & Werts, 2022), and hamsters are very susceptible to the disease and are the referent model for acute human leptospirosis (Gomes et al , 2018). We therefore showed that the lack of induced macrophage cell death upon infection with leptospires is a conserved cellular mechanism in both susceptible and resistant hosts.…”

Leptospiral Leucine-Rich Repeat Protein-Based Lateral Flow for Assessment of Canine Leptospiral Immunoglobulin G

“…This might be because the sequence of those serovars has no resemblance to rhKU_Sej_LRR_2271 (Supplementary Data S1). As is known, the severity of signs and symptoms after infection depends on the serotypes of Leptospira and its hosts [2,43]. The specific pattern recognition receptors (PRRs) such as Toll-like and NOD-like receptors, the innate immune response of hosts, molecular mimicry, and the escape of recognition of leptospires might be important factors in the differences of their immune responses [32,43,44].…”