The aim of this review is to give an outline of the blood clearance function of the liver sinusoidal endothelial cells (LSECs) in health and disease. Lining the hundreds of millions of hepatic sinusoids in the human liver the LSECs are perfectly located to survey the constituents of the blood. These cells are equipped with high-affinity receptors and an intracellular vesicle transport apparatus, enabling a remarkably efficient machinery for removal of large molecules and nanoparticles from the blood, thus contributing importantly to maintain blood and tissue homeostasis. We describe here central aspects of LSEC signature receptors that enable the cells to recognize and internalize blood-borne waste macromolecules at great speed and high capacity. Notably, this blood clearance system is a silent process, in the sense that it usually neither requires or elicits cell activation or immune responses. Most of our knowledge about LSECs arises from studies in animals, of which mouse and rat make up the great majority, and some species differences relevant for extrapolating from animal models to human are discussed. In the last part of the review, we discuss comparative aspects of the LSEC scavenger functions and specialized scavenger endothelial cells (SECs) in other vascular beds and in different vertebrate classes. In conclusion, the activity of LSECs and other SECs prevent exposure of a great number of waste products to the immune system, and molecules with noxious biological activities are effectively “silenced” by the rapid clearance in LSECs. An undesired consequence of this avid scavenging system is unwanted uptake of nanomedicines and biologics in the cells. As the development of this new generation of therapeutics evolves, there will be a sharp increase in the need to understand the clearance function of LSECs in health and disease. There is still a significant knowledge gap in how the LSEC clearance function is affected in liver disease.

SummaryOne Health is an interdisciplinary collaboration that aims at mitigating risks to human health arising from microorganisms present in non-human animal species, which have the potential to be transmitted and cause disease in humans. Different degrees of scientific collaboration and sectoral integration are needed for different types of zoonotic diseases, depending on the health and associated economic gains that can be expected from a One Health approach. Indeed, mitigating zoonotic risks related to emerging diseases with pandemic potential is different from mitigating risks related to endemic zoonotic diseases like brucellosis. Likewise, management of brucellosis at the wildlife-livestock interface in wildlife conservation areas is in essence different from mitigating transmission of a given Brucella species within its preferential host species, which in turn is different from mitigating the spillover of a given Brucella species to non-preferential host species, humans included. Brucellosis economic models often oversimplify and/or wrongly assess transmission between reservoir hosts and spillover hosts. Moreover, they may not properly value non-market outcomes, such as avoidance of human disease, consumer confidence and conservation biology issues. As a result, uncertainty is such that the economic predictions of these models can be questionable. Therefore, understanding the infection biology of Brucella species is a prerequisite. This paper reviews and highlights important features of the infection biology of Brucella species and the changing epidemiology of brucellosis that need to be integrated into a true One Health perspective of brucellosis.

Abstract.A species-independent indirect enzyme-linked immunosorbent assay (iELISA) based on chimeric protein A/G was established for the detection of anti-Brucella antibodies in Arctic wildlife species and compared to previously established brucellosis serological tests for hooded seals (Cystophora cristata), minke whales (Balaenoptera acutorostrata), sei whales (Balaenoptera borealis), fin whales (Balaenoptera physalus), and polar bears (Ursus maritimus), as well as bacteriology results for reindeer and caribou (Rangifer tarandus sp.). The protein A/G iELISA results were consistent with the other serological tests with Cohen kappa values between 0.47 and 0.92, and the protein A/G iELISA can thus offer a technically simple method for these species yielding results consistent with established brucellosis serological tests. Receiver operator characteristics analysis proved that the reindeer and caribou protein A/G iELISA results were consistent with the bacteriological gold standard with an area under the curve of 0.99, and the protein A/G iELISA was thus validated as a sensitive and specific serological method for the detection of anti-Brucella antibodies in reindeer and caribou. The binding of the antibodies from the respective species to protein A and G were also evaluated in the iELISA. The antibodies from hooded seals and polar bears reacted stronger to protein A than to G. The sei whale, fin whale, reindeer, and caribou antibodies reacted stronger to protein G than to A. The minke whale antibodies reacted to both protein A and G. There was a strong correlation (r s = 0.88-0.98) between the optical density results obtained with the iELISA with protein A/G and protein A or G, showing that protein A/G is as well suited as protein A or G for the detection of anti-Brucella antibodies in these species with the iELISA.