Investigating the Immunological and Biological Equilibrium of Reservoir Hosts and Pathogenic Leptospira: Balancing the Solution to an Acute Problem?

Abstract

Leptospirosis is a devastating zoonotic disease affecting people and animals across the globe. Pathogenic leptospires are excreted in urine of reservoir hosts which directly or indirectly leads to continued disease transmission, via contact with mucous membranes or a breach of the skin barrier of another host. Human fatalities approach 60,000 deaths per annum; though most vertebrates are susceptible to leptospirosis, complex interactions between host species and serovars of Leptospira can yield disease phenotypes that vary from asymptomatic shedding in reservoir hosts, to multiorgan failure in incidental hosts. Clinical symptoms of acute leptospirosis reflect the diverse range of pathogenic species and serovars that cause infection, the level of exposure, and the relationship of the pathogen with the given host. However, in all cases, pathogenic Leptospira are excreted into the environment via urine from reservoir hosts which are uniformly recognized as asymptomatic carriers. Therefore, the reservoir host serves as the cornerstone of persistent disease transmission. Although bacterin vaccines can be used to abate renal carriage and excretion in domestic animal species, there is an urgent need to advance our understanding of immune-mediated host-pathogen interactions that facilitate persistent asymptomatic carriage. This review summarizes the current understanding of host-pathogen interactions in the reservoir host and prioritizes research to unravel mechanisms that allow for colonization but not destruction of the host. This information is required to understand, and ultimately control, the transmission of pathogenic Leptospira.

Anti-Leptospira immunoglobulin profiling in mice reveals strain specific IgG and persistent IgM responses associated with virulence and renal colonization

“…Quite unexpectedly, around 5% of women tested harbor high and sustained levels of IgM (invalidating the diagnosis of a recent infection) supposedly due to frequent reinfections because of consumption of contaminated food, but it is also possible that it may due to asymptomatic toxoplasmosis leading upon immune depression during gestation to the reactivation of cysts in the brain and release of tachyzoites [73,74]. In the case of leptospirosis, sustained IgM responses have been recorded in dogs [75] that are known to excrete Leptospira in their urine [76]. On the other hand, only transient IgM responses have been measured in bovines experimentally infected with L. interrogans serovar Hardjo [77].…”

Genetic manipulation of pathogenic Leptospira: CRISPR interference (CRISPRi)-mediated gene silencing and rapid mutant recovery at 37 °C

“…Leptospirosis is a neglected, widespread zoonosis caused by distinct pathogenic species of the genus Leptospira , and is responsible for more than one million cases and 60,000 deaths per year worldwide 1 – 3 . Domestic and wild animal populations can be asymptomatic carriers of the pathogen, which are excreted from persistently colonized renal tubules via urine into the environment to maintain continued disease transmission 1 , 4 . Humans and other animals are infected via contact with urine of infected hosts, either directly, or indirectly through contaminated water or soil 3 .…”

Bovine Immune Response to Vaccination and Infection with Leptospira borgpetersenii Serovar Hardjo

“…Similar findings in both chronic leptospirosis infection models indicate that the local lymph nodes rather than the periphery are the sites for memory T cells. The local lymph node memory response will need to be further studied and the role of these cytokines elucidated in cattle or in other chronic infection host models such as the rat (32).…”