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.constitutive pulmonary intravascular macrophages; induced pulmonary intravascular macrophages; human lung ONE OF THE STATEMENTS FROM a workshop on pulmonary immunobiology and inflammation sponsored by the National Heart, Lung, and Blood Institute in 1999 was, "In humans, the relative roles of endothelium, pulmonary intravascular macrophages, neutrophils, or other pulmonary cells in the clearance and processing of microorganisms and antigens from the systemic venous blood are poorly defined" (15). Since then, there has been significant advancement in understanding the roles of many of the indicated cells. However, the progress has been limited for the pulmonary intravascular macrophages (PIMs). We provide a focused review of the biology of PIMs to underscore a need to study their role in human lung disease.The role of vascular inflammation in regulating the organ and systemic inflammatory responses is well established. In this context, the contributions of intravascular mononuclear phagocytes such as hepatic Kupffer cells in microbial inflammation are well understood. In contrast, the PIMs are much lesser known and appreciated for their potential influence on lung physiology. PIMs range from 20 to 80 m in diameter and typically are firmly attached to the capillary endothelium on the thicker side of the alveolar septum, presumably to minimize the impact on gas exchange, in species such as cattle, horse, sheep, goat, and pigs (56, 64). PIMs' identity as macrophages in species such as cattle and horse was confirmed in situ through phenotyping with anti-macrophage antibodies (36,49). Although sheep lung is credited with the highest concentration of PIMs, which cover 20% of the capillary endothelium (56), the horse PIMs are the largest in size. The plasma membrane of PIMs exhibits a uniquely enhanced glycocalyx through decoration with lipid or lipoprotein globules of 50 -200 nm in size (Fig.

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.

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With the rapid global spread of West Nile virus (WNV) and the endemic state it has acquired in new geographical areas, we hereby bring a thorough serological investigation of WNV in horses in a longstanding endemic region, such as Israel. This study evaluates the environmental and demographic risk factors for WNV infection in horses and suggests possible factors associated with the transition from endemic to epidemic state. West Nile virus seroprevalence in horses in Israel was determined throughout a period of more than a decade, before (1997) and after (2002 and 2013) the massive West Nile fever outbreak in humans and horses in 2000. An increase in seroprevalence was observed, from 39% (113/290) in 1997 to 66.1% (547/827) in 2002 and 85.5% (153/179) in 2013, with persistent significantly higher seroprevalence in horses situated along the Great Rift Valley (GRV) area, the major birds' migration route in Israel. Demographic risk factors included age and breed of the horse. Significantly lower spring precipitation was observed during years with increased human incidence rate that occurred between 1997–2007. Hence, we suggest referring to Israel as two WNV distinct epidemiological regions; an endemic region along the birds' migration route (GRV) and the rest of the country which perhaps suffers from cyclic epidemics. In addition, weather conditions, such as periods of spring drought, might be associated with the transition from endemic state to epidemic state of WNV.

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.

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.

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.

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