Investigating the immunological and biological equilibrium of reservoir hosts and pathogenic Leptospira: balancing the solution to an acute problem

Authors: Putz, Ellie; Nally, Jarlath

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/29/2020
Publication Date: 8/14/2020
Citation: Putz, E.J., Nally, J.E. 2020. Investigating the immunological and biological equilibrium of reservoir hosts and pathogenic Leptospira: balancing the solution to an acute problem. Frontiers in Immunology. 11:2005. https://doi.org/10.3389/fmicb.2020.02005.
DOI: https://doi.org/10.3389/fmicb.2020.02005

Interpretive Summary: Leptospirosis is a zoonotic disease affecting humans and animals around the world. Pathogenic Leptospira bacteria colonize the kidney of infected hosts, where they are shed in the urine into the environment where other individuals can then be infected directly or indirectly. While some hosts may appear completely asymptomatic, in other hosts, leptospirosis can cause severe infection including multi-organ failure and even death. Certain host species, called reservoir hosts, will carry leptospira in their kidneys and shed bacteria in their urine, but will appear completely asymptomatic of disease. Reservoir hosts are the prime carriers and spreaders of disease to humans and livestock. Two of the most common reservoir hosts are cattle and rats, which represent a common source of human exposure around the globe. This variability of disease presentation is often host and Leptospira species specific, as illustrated by reservoir hosts. To elaborate, the same strain of Leptospira may cause flu-like symptoms in the human, may cause an abortion in a cow, be fatal in hamsters, and asymptomatic in the rat. This unique host and Leptospira relationship is poorly understood, but critical to investigate in the context of developing treatment and protective technologies such as vaccines. Most published literature focuses on human cases studies, seroprevalence, and features of acute disease typically studied in the highly susceptible hamster model. In this review, we summarize existing knowledge regarding specific host and pathogen interactions and highlighted the current gap in reservoir host research in the leptospirosis literature, and what could be accomplished by emphasizing studies exploring the immunological parameters of the natural reservoir hosts. Understanding reservoir host biology and the role of chronic disease is the only way to increase our understanding of, and ultimately control, global leptospirosis.

Technical 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 mucus 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 multi-organ 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 physiology of 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. Reservoir hosts are 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 understanding of host-pathogen interactions in the reservoir host and prioritizes research to unravel immunological 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.