Publications by year


Publications by Authors

Recent Publications

Contact Us

Department of Animal Sciences
The Robert H. Smith Faculty
of Agricultural, Food & Environment

The Hebrew University of Jerusalem.

Herzl 229, Rehovot 7610001, Israel
Phone: +972-(0)8-9489119;
Fax: +972-(0)8-9465763;
Yael Lewitus, Department's Secretary


Wein, Y. ; Barshira, E. ; Friedman, A. Increased serum levels of advanced glycation end products due to induced molting in hen layers trigger a proinflammatory response by peripheral blood leukocytes. POULTRY SCIENCE 2020, 99, 3452-3462.Abstract
Induced molting (IM), a severe detriment to animal welfare, is still used in the poultry industry in some countries to increase or rejuvenate egg production and is responsible for several physiological perturbations, possibly including reactive oxidative stress, a form of metabolic stress. Because metabolic stress has been shown to induce a proinflammatory response involved in attempts to restore homeostasis, we hypothesized that similar responses followed IM. To confirm this hypothesis, we initially confirmed the establishment of oxidative stress during IM in 75-wk-old layers by demonstrating increased production of advanced glycation end products (AGE). Concomitant with increased oxidative metabolites, cellular stress was demonstrated in peripheral blood leukocytes (PBL) by increased levels of stress gene products (the glucocorticoid receptor, sirtuin-1, and heat shock protein 70 mRNA). Increased expression of stress proteins in PBL was followed by a proinflammatory response as demonstrated by increased levels of proinflammatory gene products (IL-6 and IL-1 beta mRNA); increased expression of these gene products was also demonstrated in direct response to AGE in vitro, thus establishing a direct link between oxidative and cellular stress. To establish a possible pathway for inducing a proinflammatory response by PBL, we showed that AGE increased a time dependent expression of galactin-3, Toll-like receptor-4, and nuclear factor - kappa B, all involved in the proinflammatory activation pathway. In vivo, AGE formed complexes with increased levels of circulating acute phase proteins (lysozyme and transferrin), products of a proinflammatory immune response, thereby demonstrating an effector response to cope with the consequences of oxidative stress. Thus, the harmful consequences of IM for animal welfare are extended here by demonstrating the activation of a resource-demanding proinflammatory response.
Eidelman, A. ; Cohen, C. ; Navarro-Castilla, Á. ; Filler, S. ; Gutiérrez, R. ; Bar-Shira, E. ; Shahar, N. ; Garrido, M. ; Halle, S. ; Romach, Y. ; et al. The dynamics between limited-term and lifelong coinfecting bacterial parasites in wild rodent hosts. Journal of Experimental Biology 2019, 222. Publisher's VersionAbstract
Interactions between coinfecting parasites may take various forms, either direct or indirect, facilitative or competitive, and may be mediated by either bottom-up or top-down mechanisms. Although each form of interaction leads to different evolutionary and ecological outcomes, it is challenging to tease them apart throughout the infection period. To establish the first step towards a mechanistic understanding of the interactions between coinfecting limited-term bacterial parasites and lifelong bacterial parasites, we studied the coinfection of Bartonella sp. (limited-term) and Mycoplasma sp. (lifelong), which commonly co-occur in wild rodents. We infected Bartonella- and Mycoplasma-free rodents with each species, and simultaneously with both, and quantified the infection dynamics and host responses. Bartonella benefited from the interaction; its infection load decreased more slowly in coinfected rodents than in rodents infected with Bartonella alone. There were no indications for bottom-up effects, but coinfected rodents experienced various changes, depending on the infection stage, in their body mass, stress levels and activity pattern, which may further affect bacterial replication and transmission. Interestingly, the infection dynamics and changes in the average coinfected rodent traits were more similar to the chronic effects of Mycoplasma infection, whereas coinfection uniquely impaired the host’s physiological and behavioral stability. These results suggest that parasites with distinct life history strategies may interact, and their interaction may be asymmetric, non-additive, multifaceted and dynamic through time. Because multiple, sometimes contrasting, forms of interactions are simultaneously at play and their relative importance alternates throughout the course of infection, the overall outcome may change under different ecological conditions. © 2019. Published by The Company of Biologists Ltd.
Barshira, E. ; Friedman, A. Innate immune functions of avian intestinal epithelial cells: Response to bacterial stimuli and localization of responding cells in the developing avian digestive tract. PLoS One 2018, 13, e0200393.Abstract
Intestinal epithelial cells are multi-tasked cells that participate in digestion and absorption as well as in protection of the digestive tract. While information on the physiology and immune functions of intestinal epithelial cells in mammals is abundant, little is known of their immune function in birds and other species. Our main objectives were to study the development of anti-bacterial innate immune functions in the rapidly developing gut of the pre- and post-hatch chick and to determine the functional diversity of epithelial cells. After establishing primary intestinal epithelial cell cultures, we demonstrated their capacity to uptake and process bacteria. The response to bacterial products, LPS and LTA, induced expression of pro-inflammatory cytokine genes (IL-6, IL-18) as well as the expression of the acute phase proteins avidin, lysozyme and the secretory component derived from the polymeric immunoglobulin receptor. These proteins were then localized in gut sections, and the goblet cell was shown to store avidin, lysozyme as well as secretory component. Lysozyme staining was also located in a novel rod-shaped intestinal cell, situated at different loci along the villus, thus deviating from the classical Paneth cell in the mammal, that is restricted to crypts. Thus, in the chicken, the intestinal epithelium, and particularly goblet cells, are committed to innate immune protection. The unique role of the goblet cell in chicken intestinal immunity, as well as the unique distribution of lysozyme-positive cells highlight alternative solutions of gut protection in the bird.
Wein, Y. ; Geva, Z. ; Bar-Shira, E. ; Friedman, A. Transport-related stress and its resolution in turkey pullets: activation of a pro-inflammatory response in peripheral blood leukocytes. Poultry Science 2017, 96, 2601 - 2613. Publisher's VersionAbstract
The transportation process is one of the most stressful practices in poultry and livestock management. Extensive knowledge is available on the impact of transport on stress and animal welfare; however, little is known on the impact of transport on the physiology of turkey pullets, their welfare and health, and even less on the process of homeostatic recovery in the post-transport new environment. The main focus of this manuscript was to focus on trauma, stress, and recovery following transport of turkey pullets from nurseries to pullet farms. Specifically, we determined the physiological consequences of transport, the temporal restoration of homeostasis and its effects on immune system function. We hypothesized that stress signaling by stress hormones would directly activate circulating turkey blood leukocytes (TBL), thus inducing a pro-inflammatory response directed towards tissue repair and recovery. Extensive blood analyses prior to transit and during the collecting, transit, and post-transit stages revealed extensive stress (elevated heat shock protein 70) and blunt-force trauma (internal bleeding and muscle damage as well as limb fractures). TBL were shown to increase mRNA expression of cortisol and adrenergic receptors during transit, thus indicating a possible direct response to circulating stress hormones. Consequently, TBL were shown to increase mRNA expression of pro-inflammatory cytokines, as well as that of serum inflammatory proteins (lysozyme and transferrin) partaking in reducing oxygen radicals as demonstrated by consumption of these proteins. The flare-up due to transit related stress diminished with time until 10 d post-transit, a time at which most parameters returned to resting levels. Though general and vaccine-specific antibody levels were not altered by transport-related stress, the physical and physiological injury caused during transport may explain the susceptibility of turkey pullets to opportunist pathogens in the immediate post-transit period.
Wein, Y. ; Barshira, E. ; Friedman, A. Avoiding handling-induced stress in poultry: use of uniform parameters to accurately determine physiological stress. Poultry Scienceps 2016, 96, 65 - 73. Publisher's VersionAbstract
Due to increase in awareness of poultry welfare and concomitant legislation, it has become necessary to determine poultry's response to stress, with minimal harm and maximum reliability. Several methods to determine the response to physiological stress were developed throughout the years to identify stressors and to measure stress in poultry. The most commonly used are plasma corticosterone levels and peripheral blood heterophil/lymphocyte ratio (H/L ratio). However, the value of these responses to determine a state of stress has been questioned in several instances, as these parameters are increased during the process of bird handling and blood sampling irrespective of the general state of stress. Due to these limitations, it appears that the classic stress markers might be sub-optimal in evaluating stress in poultry, particularly those encountered in high-stress environments. Thus, there is a continuing need for stress indicators, preferably indicators that are quantitative, highly repeatable, not influenced by handling and sampling, determined in peripheral blood, represent an initial response to the stressor, and do not daily fluctuate. As the immune system has been shown to rapidly respond to stress, we assessed pro-inflammatory gene expression in peripheral blood cells as an indicator for stress. We initially show that while corticosterone plasma levels and the H/L ratio were responsive to handling and blood sampling, pro-inflammatory gene expression (lysozyme, IL-1β, IL-6, and HSP-70) was not. We then determined the expression of the same pro-inflammatory genes during acute stress (transit) in layer pullets (hen and turkey) and during chronic stress (different caging densities of layers utilizing 2, 3, and 4 hens/cage). While gene expression was significantly and highly elevated during transit, the effect of differing caging densities on gene expression was minimal; collectively, this might indicate that expression of pro-inflammatory genes is more responsive to acute stress than to chronic stressors. We propose to use pro-inflammatory gene expression in peripheral blood cells to measure responses to stress in poultry.
Warburton, E. M. ; Kam, M. ; Bar-Shira, E. ; Friedman, A. ; Khokhlova, I. S. ; Koren, L. ; Asfur, M. ; Geffen, E. ; Kiefer, D. ; Krasnov, B. R. ; et al. Effects of parasite pressure on parasite mortality and reproductive output in a rodent-flea system: inferring host defense trade-offs. 2016, 115, 3337 - 3344. Publisher's VersionAbstract
Evaluating host resistance via parasite fitness helps place host-parasite relationships within evolutionary and ecological contexts; however, few studies consider both these processes simultaneously. We investigated how different levels of parasite pressure affect parasite mortality and reproductive success in relationship to host defense efforts, using the rodent Gerbillus nanus and the flea Xenopsylla conformis as a host-parasite system. Fifteen immune-naïve male rodents were infested with 20, 50, or 100 fleas for four weeks. During this time number of new imagoes produced per adult flea (our flea reproductive output metric), flea mortality, and change in circulating anti-flea immunoglobulin G (our measure of adaptive immune defense) were monitored. Three hypotheses guided this work: (1) increasing parasite pressure would heighten host defenses; (2) parasite mortality would increase and parasite reproductive output would decrease with increasing investment in host defense; and (3) hosts under high parasite pressure could invest in behavioral and/or immune responses. We predicted that at high infestation levels (a) parasite mortality would increase; (b) flea reproductive output per individual would decrease; and (c) host circulating anti-flea antibody levels would increase. The hypotheses were partially supported. Flea mortality significantly increased and flea reproductive output significantly decreased as flea pressure increased. Host adaptive immune defense did not significantly change with increasing flea pressure. Therefore, we inferred that investment in host behavioral defense, either alone or in combination with density-dependent effects, may be more efficient at increasing flea mortality and decreasing flea reproductive output than antibody production during initial infestation in this system.