Nahum Y Shpigel

Publications (12)42.43 Total impact

• Article: Comparison of the epidemiology of epizootic haemorrhagic disease and bluetongue viruses in dairy cattle in Israel.

  Maor Kedmi, Nadav Galon, Yael Herziger, Hagai Yadin, Velizar Bombarov, Carrie Batten, Nahum Y Shpigel, Eyal Klement
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  ABSTRACT: An outbreak of epizootic haemorrhagic disease virus (EHDV) in cattle in Israel in 2006 enabled a comparison of the spatial distribution of epidemic exposure to EHDV with that of exposure to bluetongue virus (BTV), which is endemic in the country. The seroprevalence of both viruses was examined in 1650 serum samples collected from 139 farms representative of the spatial distribution of dairy cattle in Israel. A significant association between exposure to EHDV and BTV was demonstrated in both univariate and multivariate analyses. Recent exposure to BTV and EHDV (demonstrated by seroprevalence in calves) was clustered in different geographical locations, indicating that the two viruses had different patterns of spread, that of EHDV being influenced by winds and terrain barriers and that of BTV by herd immunity.
  The Veterinary Journal 11/2010; 190(1):77-83. · 2.24 Impact Factor
• Article: Enterohemorrhagic Escherichia coli induce attaching and effacing lesions and hemorrhagic colitis in human and bovine intestinal xenograft models.

  Lilach Golan, Erez Gonen, Simcha Yagel, Ilan Rosenshine, Nahum Y Shpigel
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  ABSTRACT: Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important cause of diarrhea, hemorrhagic colitis and hemolytic uremic syndrome in humans worldwide. The two major virulence determinants of EHEC are the Shiga toxins (Stx) and the type III secretion system (T3SS), including the injected effectors. Lack of a good model system hinders the study of EHEC virulence. Here, we investigated whether bovine and human intestinal xenografts in SCID mice can be useful for studying EHEC and host tissue interactions. Fully developed, germ-free human and bovine small intestine and colon were established by subcutaneous transplantation of human and bovine fetal gut into SCID mice. Xenografts were allowed to develop for 3-4 months and thereafter were infected by direct intraluminal inoculation of Stx-negative derivatives of EHEC O157:H7, strain EDL933. The small intestine and colon xenografts closely mimicked the respective native tissues. Upon infection, EHEC induced formation of typical attaching and effacing lesions and tissue damage that resembled hemorrhagic colitis in colon xenografts. By contrast, xenografts infected with an EHEC mutant deficient in T3SS remained undamaged. Furthermore, EHEC did not attach to or damage the epithelium of small intestinal tissue, and these xenografts remained intact. EHEC damaged the colon in a T3SS-dependent manner, and this model is therefore useful for studying the molecular details of EHEC interactions with live human and bovine intestinal tissue. Furthermore, we demonstrate that Stx and gut microflora are not essential for EHEC virulence in the human gut.
  Disease Models and Mechanisms 10/2010; 4(1):86-94. · 4.94 Impact Factor
• Source

  Available from: PubMed Central

  Article: Essential role of neutrophils but not mammary alveolar macrophages in a murine model of acute Escherichia coli mastitis.

  Sharon Elazar, Erez Gonen, Ayala Livneh-Kol, Ilan Rosenshine, Nahum Y Shpigel
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  ABSTRACT: Mastitis, the inflammation of the mammary gland, is an important disease affecting dairy animals worldwide. The disease is caused by mammary pathogenic bacteria and Escherichia coli are frequently implicated. Virulence factors of mammary pathogenic E. coli are only partially known and intramammary challenge with LPS elicits neutrophil recruitment in experimental bovine and murine mastitis models. We have previously shown that neutrophil recruitment in LPS-induced murine mastitis is strictly dependent on mammary alveolar macrophages. However, the relative role of alveolar macrophages and blood neutrophils in E. coli mastitis is not well defined. To this end, we selectively depleted mammary alveolar macrophages or blood neutrophils before intramammary challenge with E. coli strain P4 (ECP4). Mice depleted of alveolar macrophages prior to intramammary challenge recruited neutrophils normally and restricted bacterial growth and interstitial invasion. Importantly however, upon depletion of alveolar macrophages, ECP4 invaded the mammary alveolar epithelial cells and formed intracellular bacterial communities. In contrast, neutrophil depletion prior to intramammary infection with ECP4 was associated with unrestricted bacterial growth, tissue damage, severe sepsis and mortality. This study suggests that neutrophils but not alveolar macrophages provide essential antimicrobial defense against mammary pathogenic E. coli. Furthermore, we show here similar invasion after depletion of alveolar macrophages as in our previous studies showing that LPS/TLR4 signaling on alveolar macrophages abrogates ECP4 invasion of the mammary epithelium. Interestingly, similar ECP4 invasion and formation of intracellular communities were also observed following intramammary infection of either iNOS gene-deficient or IL-1 receptor type 1 gene-deficient mice.
  Veterinary Research 04/2010; 41(4):53. · 4.06 Impact Factor
• Article: Beta-hydroxybutyrate abrogates formation of bovine neutrophil extracellular traps and bactericidal activity against mammary pathogenic Escherichia coli.

  Navit Grinberg, Sharon Elazar, Ilan Rosenshine, Nahum Y Shpigel
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  ABSTRACT: Escherichia coli is an important bacterial species isolated from bovine mastitis. The rate of neutrophil recruitment into the mammary gland and their bactericidal activity largely affect the severity and outcome of the disease. Ketosis is a common metabolic disease, and affected dairy cows are known to have increased risk for mastitis and other infectious conditions. The disease is associated with high blood and milk levels of beta-hydroxybutyrate (BHBA), previously shown to negatively affect neutrophil function by unknown mechanisms. We show here that the mammary pathogenic E. coli strain P4 activates normal bovine neutrophils to form neutrophil extracellular traps (NETs), which are highly bactericidal against this organism. Preincubation of these neutrophils with increasing concentrations (0.1 to 8 mmol/liter) of BHBA caused a fivefold decrease of E. coli P4 phagocytosis, though intracellular killing was unaffected. Furthermore, BHBA caused a 10-fold decrease in the NETs formed by E. coli P4-activated neutrophils and a similar decrease in NET bactericidal activity against this organism. These negative effects of BHBA on bovine neutrophils might explain the increased susceptibility of ketotic cows to mastitis and other infectious conditions.
  Infection and immunity 07/2008; 76(6):2802-7. · 4.21 Impact Factor
• Article: Mammary pathogenic Escherichia coli.

  Nahum Y Shpigel, Sharon Elazar, Ilan Rosenshine
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  ABSTRACT: Pathogenic Escherichia coli can be classified into several pathotypes, and it is believed that each pathotype carries one or more specific gene repertoire (or virulence factors combination) that distinguishes them from non-pathogenic E. coli strains and from other pathotypes. In contrast to this notion, it was proposed that this is not the case for E. coli mastitis, a common disease in farm animals and that any given E. coli isolate can cause this disease, even strains that are considered non-pathogenic. In this review we will re-examine this latter concept and recent advances in the study E. coli mastitis.
  Current Opinion in Microbiology 03/2008; 11(1):60-5. · 7.93 Impact Factor
• Article: Toll-like receptor 4 is needed to restrict the invasion of Escherichia coli P4 into mammary gland epithelial cells in a murine model of acute mastitis.

  Erez Gonen, Alexandra Vallon-Eberhard, Sharon Elazar, Alon Harmelin, Ori Brenner, Ilan Rosenshine, Steffen Jung, Nahum Y Shpigel
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  ABSTRACT: Mastitis, an inflammatory response of the mammary tissue to invading pathogenic bacteria, is a common disease in breast-feeding women and dairy animals. Escherichia coli is a leading cause of mastitis in dairy animals. During the course of the disease the host mounts a strong inflammatory response, but specific bacterial virulence factors have not yet been identified. Here we report the use of a murine mastitis model to investigate the innate inflammatory reaction of the mammary gland. We show that lipopolysaccharide (LPS) infusion induces mastitis in wild-type mice (C3H/HeN), but not in mice expressing mutated Toll-like receptor 4 (TLR4) (C3H/HeJ). The wild-type phenotype was restored by adoptive transfer of TLR4-expressing macrophages into the alveolar milk space of C3H/HeJ mice. In contrast to the LPS treatment, infection with E. coli P4 (ECP4) resulted in inflammation even in the absence of LPS/TLR4 signalling, indicating that additional factors play a role in the pathogenesis of the intact bacteria. Furthermore, in the absence of functional TLR4 the infecting ECP4 invade the epithelial cells with high efficiency, forming intracellular microcolonies. However, adoptive transfer with TLR4-expressing macrophages drastically reduced the epithelial invasion. Taken together, these results indicate that ECP4 has an invasive potential, which is restricted by alveolar macrophages in response to the LPS/TLR4 signalling.
  Cellular Microbiology 01/2008; 9(12):2826-38. · 5.46 Impact Factor
• Article: Presence of antibotulinum neurotoxin antibodies in selected wild canids in Israel.

  Amir Steinman, Neta Millet, Chana Frenkel, Roni King, Nahum Y Shpigel
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  ABSTRACT: Serum samples from 35 golden jackals (Canis aureus syriacus), eight wolves (Canis lupus), and four red foxes (Vulpes vulpes) from various regions of Israel were collected during the years 2001-04 and tested for antibodies to Clostridium botulinum neurotoxin (BoNT) types C and D. Antibodies against BoNT types C and D were detected in 10 (29%) and in 3 (9%) of 35 golden jackals, respectively, using enzyme-linked immunosorbent assay. This report describes detection of anti BoNT antibodies in wild canids other than coyotes (Canis latrans) for the first time and demonstrates that C. botulinum type C is prevalent in Israel.
  Journal of wildlife diseases 08/2007; 43(3):548-50. · 1.08 Impact Factor
• Article: Evaluation of intrauterine antibiotic treatment of clinical metritis and retained fetal membranes in dairy cows.

  Tamir Goshen, Nahum Y Shpigel
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  ABSTRACT: Retained fetal membranes (RFM) and clinical metritis (CM) are frequently diagnosed disease conditions in dairy cows and considered of major economic impact due to negative effect on reproduction and milk production. The objective of this study was to evaluate the efficacy of i.u. tetracycline for the treatment of RFM and CM in dairy cows. Affected cows were randomly assigned to two groups; treatment group animals received i.u. 5g chlortetracycline twice weekly for 2 wks, and no treatment group. A total of 1416 cows and 804 heifers in 5 herds calved during the study period. CM was diagnosed in 18.6% (inter farm range; 15.2-23.5%) and 30% (19.4-42.3%) of cows and heifers, respectively. RFM was diagnosed in 13.1% (9.4-18.1%) and 9.2% (3.6-13.8%) of cows and heifers, respectively. Conception rates after first insemination were 38.3%, 42.5% and 18% in normal, treated and non-treated CM cows, respectively. Numbers of days open were 140.5, 136.2 and 165.5 in normal, treated and non-treated CM cows, respectively. Based on 305-d corrected milk yield, cows and heifers affected by RFM and CM produced 300-500kg less milk compared with their normal herd mates. Cows treated for CM produced 654kg more milk per 305-d corrected lactation compared to non-treated control cows. Treatment of RFM had no effect on reproductive performance or milk production. In conclusion, i.u. chlortetracycline treatment was proven to prevent the detrimental effect of CM on reproductive performance in heifers and cows and on milk production in cows only.
  Theriogenology 01/2007; 66(9):2210-8. · 1.96 Impact Factor
• Article: Experimental infection of common garter snakes (Thamnophis sirtalis) with West Nile virus.

  Amir Steinman, Caroline Banet-Noach, Lubov Simanov, Nurit Grinfeld, Zachi Aizenberg, Ohad Levi, Dan Lahav, Mertyn Malkinson, Shimon Perk, Nahum Y Shpigel
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  ABSTRACT: The role of various reptilian species in the infectious cycle of several arboviruses is documented, but their role in that of West Nile virus (WNV) is uncertain. Common garter snakes (Thamnophis sirtalis) were infected subcutaneously with 10(5) plaque forming units (PFU) WNV-Isr 98, five of nine snakes became viremic, and five exhibited persistent low levels of neutralizing antibodies. Four of the parentally infected snakes died and high titers of virus were found in multiple organ samples. In contrast, orally infected garter snakes did not become viremic, but viral RNA was detected in cloacal swabs. Since oral infection of predator birds by WNV is known, their ingestion of infected snakes may also result in their becoming infected.
  Vector Borne and Zoonotic Diseases 02/2006; 6(4):361-8. · 2.44 Impact Factor
• Article: CD44 is highly expressed on milk neutrophils in bovine mastitis and plays a role in their adhesion to matrix and mammary epithelium.

  Erez Gonen, Shlomo Nedvetzki, David Naor, Nahum Y Shpigel
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  ABSTRACT: Mastitis, inflammation of the mammary gland, is a common and economically important disease in dairy animals. Mammary pathogenic organisms, such as Escherichia coli, invade the teat canal,milk ducts, and mammary alveolar space, replicate in mammary secretions, and elicit a local inflammatory response characterized by massive recruitment of blood polymorphonuclear neutrophil leukocytes (PMN) into the alveoli and milk ducts. CD44 is a trans-membrane glycoprotein previously shown to play a role in mediation and control of blood PMN recruitment in response to inflammatory signals. Here we show, for the first time, increased expression of CD44 on recruited milk PMN in bovine mastitis and the expression of a CD44 variant, CD44v10, on these PMN. Furthermore, we demonstrate that CD44 mediates specific adhesion of bovine blood PMN to hyaluronic acid and mammary epithelial cells. Our results suggest that in mastitis CD44 plays a role in recruiting blood PMN into the mammary glands, the exact nature of this role needs to be elucidated.
  Veterinary Research 39(3):29. · 4.06 Impact Factor
• Article: Essential role of neutrophils but not mammary alveolar macrophages in a murine model of acute

  Sharon Elazar, Erez Gonen, Ayala Livneh-Kol, Ilan Rosenshine, Nahum Y Shpigel
  http://dx.doi.org/10.1051/vetres/2010025.
• Article: Mathematical modelling and evaluation of the different routes of transmission of lumpy skin disease virus.

  Reuma Magori-Cohen, Yoram Louzoun, Yael Herziger, Eldad Oron, Alon Arazi, Eeva Tuppurainen, Nahum Y Shpigel, Eyal Klement
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  ABSTRACT: ABSTRACT: Lumpy skin disease (LSD) is a severe viral disease of cattle. Circumstantial evidence suggests that the virus is transmitted mechanically by blood-feeding arthropods. We compared the importance of transmission via direct and indirect contact in field conditions by using mathematical tools. We analyzed a dataset collected during the LSD outbreak in 2006 in a large dairy herd, which included ten separated cattle groups. Outbreak dynamics and risk factors for LSD were assessed by a transmission model. Transmission by three contact modes was modelled; indirect contact between the groups within a herd, direct contact or contact via common drinking water within the groups and transmission by contact during milking procedure. Indirect transmission was the only parameter that could solely explain the entire outbreak dynamics and was estimated to have an overall effect that was over 5 times larger than all other possible routes of transmission, combined. The R0 value induced by indirect transmission per the presence of an infectious cow for 1 day in the herd was 15.7, while the R0 induced by direct transmission was 0.36. Sensitivity analysis showed that this result is robust to a wide range of assumptions regarding mean and standard deviation of incubation period and regarding the existence of sub-clinically infected cattle. These results indicate that LSD virus spread within the affected herd could hardly be attributed to direct contact between cattle or contact through the milking procedure. It is therefore concluded that transmission mostly occurs by indirect contact, probably by flying, blood-sucking insects. This has important implications for control of LSD.
  Veterinary Research 43(1):1. · 4.06 Impact Factor