Karin Aharonson-Raz

Monocyte and macrophage heterogeneity and Toll-like receptors in the lung

Mononuclear phagocytes are crucial components of the innate host defense system. Cells such as macrophages and monocytes phagocytose and process pathogens, produce inflammatory mediators, and link the innate and the adaptive immune systems. The role of innate immune receptors such as Toll-like receptors (TLRs) in the recognition of pathogens is critical for mounting a precise and targeted immune response. This review focuses attention on the development of monocytes and macrophages, various populations of macrophages, and the expression and function of TLRs on macrophages.

Pulmonary intravascular macrophages and lung health: What are we missing?

Pulmonary intravascular macrophages (PIMs) are constitutively found in species such as cattle, horse, pig, sheep, goat, cats, and whales and can be induced in species such as rats, which normally lack them. It is believed that human lung lacks PIMs, but there are previous suggestions of their induction in patients suffering from liver dysfunction. Recent data show induction of PIMs in bile-duct ligated rats and humans suffering from hepato-pulmonary syndrome. Because constitutive and induced PIMs are pro-inflammatory in response to endotoxins and bacteria, there is a need to study their biology in inflammatory lung diseases such as sepsis, asthma, chronic obstructive pulmonary diseases, or hepato-pulmonary syndrome. We provide a review of PIM biology to make an argument for increased emphasis and better focus on the study of human PIMs to better understand their potential role in the pathophysiology and mechanisms of pulmonary diseases.

Isolation and Phylogenetic Grouping of Equine Encephalosis Virus in Israel

During 2008–2009 in Israel, equine encephalosis virus (EEV) caused febrile outbreaks in horses. Phylogenetic analysis of segment 10 of the virus strains showed that they form a new cluster; analysis of segment 2 showed ≈92% sequence identity to EEV-3, the reference isolate. Thus, the source of this emerging EEV remains uncertain.

Molecular characterization of the Babesia caballi rap-1 gene and epidemiological survey in horses in Israel.

Equine piroplasmosis imposes great concerns for the equine industry regarding international horse movement, and therefore requires reliable diagnostic tools. Recent studies from South Africa and Jordan, including a preliminary study in Israel, reported extremely low seroprevalence to Babesia caballi (B. caballi) (0-1%) using the acceptable rhoptry-associated protein-1 (RAP-1) cELISA. In accordance with the study from South Africa demonstrating a significant heterogeneity in the rap-1 gene sequence of South African B. caballi isolates, the objectives of this study were to phylogenetically characterize the rap-1 gene of the Israeli isolates and determine the prevalence of B. caballi in horses in Israel. Out of 273 horses tested using the RAP-1 cELISA, only one was sero-positive, while 9.3% were positive on PCR performed on the rap-1 gene. Phylogenetic analysis of the rap-1 gene grouped the Israeli isolates in a cluster together with the South African strains (99% nt identity), but in a separate cluster from the American/Caribbean strains (81-82% nt identity). These findings support the existence of heterogeneity in the RAP-1 amino-acid sequences of the Israeli and South African isolates as compared to that used in the cELISA commercial kit and raise doubts as to the ability of this assay to serve as a sole regulatory test for international horse movement. Risk factor analysis found management and age to significantly associate with prevalence of B. caballi, as higher prevalence was noted in horses held out on pasture and a negative association was recorded with age. In addition, B. caballi was not detected in horses in the steppe-arid and extreme-arid climatic regions as compared to the wetter regions. Findings of this study emphasize the need to combine several detection methods to ameliorate the control and spread of the disease.

Novel description of force of infection and risk factors associated with Theileria equi in horses in Israel and in The Palestinian Authority.

The objectives of this study were to determine the force of infection (FOI) for Theileria equi in horses in Israel and to evaluate risk factors associated with seroprevalence a decade after it was last determined by PCR, in 2002. Using a commercial cELISA kit, we demonstrated a widespread and constant exposure to T. equi in Israel (110/216; 50.9%) and the Palestinian Authority (32/108; 29.6%). Owing to the paired samples collected from the same horses approximately one year apart, we were able to determine the FOI rate with which susceptible individuals become infected. Out of the 75 naïve horses in the first collection, four seroconverted during 10-16 months, demonstrating an FOI of 5% for that period. Similar results were obtained by calculating FOI using age-specific seroprevalence (4.2% per year). Housing management type was significantly associated with T. equi seroprevalence with 87.9% seropositivity in horses on pasture and 32.6% seropositivity in horses in stalls/yards. This strong association and the very high seroprevalence found in horses held on pasture, prompted stratification of data accordingly. Geographical location of horses in Israel showed a strong association with seroprevalence to T. equi ranging from 34.5% in central Israel to 80.8% in the northern part of the country. However, when analyzing this association only in horses held in stalls/yards, the lower seroprevalence was noted in the north. In addition, age was significantly associated with seroprevalence for T. equi only in horses held in stalls/yards (R(2)=0.94). Environmental variables were not found to be associated with seroprevalence for T. equi. Here, we report for the first time the FOI for T. equi in horses and highlight the influence housing management type has on the evaluation of risk factors associated with a vector-borne disease, perhaps leading to the discrepancies observed between studies throughout the world.

Analysis of the Association of Climate, Weather and Herd Immunity with the Spread of Equine Encephalosis Virus in Horses in Israel

It is claimed that the distribution of Culicoides-borne viruses is highly influenced by climate. Equine encephalosis virus (EEV) is a Culicoides-borne orbivirus which affects horses and was recently found to be endemic in Israel. To test whether climate is a crucial factor in the geographical distribution of EEV, we collected blood samples from horses in Israel during the years 2002, 2007 and 2010 and tested them for the abundance of antibodies to EEV. Samples were also collected in 2011 from horses that were seronegative to the virus in 2010, to determine the rate of infection with EEV. It was found that seroprevalence fluctuated between the years and that in each year it was highest in a different climatic region. Interestingly, analysis of infection rate at the different farms showed a negative association with seroprevalence at prior observations. In addition, analysis of precipitation preceding the outbreak of EEV which occurred during 2008 revealed that an extremely dry period existed several months prior to the febrile outbreak with the average precipitation of spring 2008 being significantly lower than the average spring precipitation of the years 1997-2009. It is therefore conjectured that exposure to EEV is not climate specific. Rather, it is highly influenced by herd immunity and weather fluctuations which might change annually. This finding may have important implications for the prediction of the abundance of Culicoides-borne viruses in endemic regions.

Low Seroprevalence of Leishmania infantum and Toxoplasma gondii in the Horse Population in Israel

A cross-sectional investigation was done on the seroprevalence of Leishmania infantum and Toxoplasma gondii infection among apparently healthy horses in Israel. This survey included 383 horses distributed in 22 farms throughout Israel during the years 2011-2013. Serum samples were tested for the presence of immunoglobulin G (IgG) antibodies using the direct agglutination test (DAT) specific to Leishmania and by the modified agglutination test (MAT) for the presence of IgG antibodies to T. gondii. Low seroprevalences were detected for both L. infantum and T. gondii in the horse population in Israel; of the 338 horses tested, 6 (1.4%) were found to be seropositive for L. infantum and 11 (2.5%) for T. gondii, with no significant association between seroprevalence and demographic/environmental factors. An ongoing geographical expansion of L. infantum, previously reported in humans and dogs in Israel, was also supported by our results in horses. Here we present evidence of exposure of horses to L. infantum and T. gondii in Israel. Continuous seroprevalence surveillance in horses, such as the one performed in this study, might further elucidate the eco-epidemiology of these two important zoonotic parasites in this country.