Control Of Parasite Burden Research Articles

Parasitological examination results of zoo animals in Germany between 2012 and 2022

Parasitic infections in zoo animals are a critical concern for both animal health and management. The aim of this study was to assess the occurrence of endo- and ectoparasites among zoo animals in Germany. A retrospective analysis of the submitted samples of a diverse range of zoo animals (5768) from a ten-year period (2012–2022) was conducted. Overall, 31.1% of those samples tested positive for at least one parasite. In the examined samples, helminths (28.4%) were found more often than protozoans (10.3%) or ectoparasites (0.8%). Among the various animal groups the following parasites were found most commonly: Artiodactyla: Coccidia (34.6%), Strongylida (23.4%); Perissodactyla: Strongylida (19.3%), Ascaridida (12.0%); Carnivora: Ascaridida (16.6%), Coccidia (8.1%); Rodentia: Oxyurida (18.2%), Coccidia (10.5%); Marsupialia: Coccidia (9.4%), Oxyurida (5.9%); Primates: Trichuris spp. (9.7%), Oxyurida (2.2%); Aves: Capillaria (7.8%), Ascaridida (7.6%); Reptilia, Amphibia, Insecta: Oxyurida (18.7%); Pisces: Ciliates (6.2%). Furthermore, potentially zoonotic parasites were identified, including Toxoplasma gondii (0.1%), Cryptosporidium sp. (0.1%). By examining the occurrence of specific parasites, these findings demonstrate the importance of parasites in the context of zoo animal health. They also highlight the need for effective strategies to control parasite burden to improve the overall welfare of zoo animals.

Eosinophils mediate SIgA production triggered by TLR2 and TLR4 to control Ascaris suum infection in mice.

Human ascariasis is the most prevalent but neglected tropical disease in the world, affecting approximately 450 million people. The initial phase of Ascaris infection is marked by larval migration from the host’s organs, causing mechanical injuries followed by an intense local inflammatory response, which is characterized mainly by neutrophil and eosinophil infiltration, especially in the lungs. During the pulmonary phase, the lesions induced by larval migration and excessive immune responses contribute to tissue remodeling marked by fibrosis and lung dysfunction. In this study, we investigated the relationship between SIgA levels and eosinophils. We found that TLR2 and TLR4 signaling induces eosinophils and promotes SIgA production during Ascaris suum infection. Therefore, control of parasite burden during the pulmonary phase of ascariasis involves eosinophil influx and subsequent promotion of SIgA levels. In addition, we also demonstrate that eosinophils also participate in the process of tissue remodeling after lung injury caused by larval migration, contributing to pulmonary fibrosis and dysfunction in re-infected mice. In conclusion, we postulate that eosinophils play a central role in mediating host innate and humoral immune responses by controlling parasite burden, tissue inflammation, and remodeling during Ascaris suum infection. Furthermore, we suggest that the use of probiotics can induce eosinophilia and SIgA production and contribute to controlling parasite burden and morbidity of helminthic diseases with pulmonary cycles.

Astrocytes promote a protective immune response to brain Toxoplasma gondii infection via IL-33-ST2 signaling.

It is of great interest to understand how invading pathogens are sensed within the brain, a tissue with unique challenges to mounting an immune response. The eukaryotic parasite Toxoplasma gondii colonizes the brain of its hosts, and initiates robust immune cell recruitment, but little is known about pattern recognition of T. gondii within brain tissue. The host damage signal IL-33 is one protein that has been implicated in control of chronic T. gondii infection, but, like many other pattern recognition pathways, IL-33 can signal peripherally, and the specific impact of IL-33 signaling within the brain is unclear. Here, we show that IL-33 is expressed by oligodendrocytes and astrocytes during T. gondii infection, is released locally into the cerebrospinal fluid of T. gondii-infected animals, and is required for control of infection. IL-33 signaling promotes chemokine expression within brain tissue and is required for the recruitment and/or maintenance of blood-derived anti-parasitic immune cells, including proliferating, IFN-γ-expressing T cells and iNOS-expressing monocytes. Importantly, we find that the beneficial effects of IL-33 during chronic infection are not a result of signaling on infiltrating immune cells, but rather on radio-resistant responders, and specifically, astrocytes. Mice with IL-33 receptor-deficient astrocytes fail to mount an adequate adaptive immune response in the CNS to control parasite burden-demonstrating, genetically, that astrocytes can directly respond to IL-33 in vivo. Together, these results indicate a brain-specific mechanism by which IL-33 is released locally, and sensed locally, to engage the peripheral immune system in controlling a pathogen.

Liver stage malaria infection is controlled by host regulators of lipid peroxidation

The facets of host control during Plasmodium liver infection remain largely unknown. We find that the SLC7a11-GPX4 pathway, which has been associated with the production of reactive oxygen species, lipid peroxidation, and a form of cell death called ferroptosis, plays a critical role in control of Plasmodium liver stage infection. Specifically, blocking GPX4 or SLC7a11 dramatically reduces Plasmodium liver stage parasite infection. In contrast, blocking negative regulators of this pathway, NOX1 and TFR1, leads to an increase in liver stage infection. We have shown previously that increased levels of P53 reduces Plasmodium LS burden in an apoptosis-independent manner. Here, we demonstrate that increased P53 is unable to control parasite burden during NOX1 or TFR1 knockdown, or in the presence of ROS scavenging or when lipid peroxidation is blocked. Additionally, SLC7a11 inhibitors Erastin and Sorafenib reduce infection. Thus, blocking the host SLC7a11-GPX4 pathway serves to selectively elevate lipid peroxides in infected cells, which localize within the parasite and lead to the elimination of liver stage parasites.

The Rough Guide to Monocytes in Malaria Infection.

While half of the world's population is at risk of malaria, the most vulnerable are still children under five, pregnant women and returning travelers. Anopheles mosquitoes transmit malaria parasites to the human host; but how Plasmodium interact with the innate immune system remains largely unexplored. The most recent advances prove that monocytes are a key component to control parasite burden and to protect host from disease. Monocytes' protective roles include phagocytosis, cytokine production and antigen presentation. However, monocytes can be involved in pathogenesis and drive inflammation and sequestration of infected red blood cells in organs such as the brain, placenta or lungs by secreting cytokines that upregulate expression of endothelial adhesion receptors. Plasmodium DNA, hemozoin or extracellular vesicles can impair the function of monocytes. With time, reinfections with Plasmodium change the relative proportion of monocyte subsets and their physical properties. These changes relate to clinical outcomes and might constitute informative biomarkers of immunity. More importantly, at the molecular level, transcriptional, metabolic or epigenetic changes can “prime” monocytes to alter their responses in future encounters with Plasmodium. This mechanism, known as trained immunity, challenges the traditional view of monocytes as a component of the immune system that lacks memory. Overall, this rough guide serves as an update reviewing the advances made during the past 5 years on understanding the role of monocytes in innate immunity to malaria.

Inflammatory and Pro-resolving Lipids in Trypanosomatid Infections: A Key to Understanding Parasite Control.

Pathogenic trypanosomatids (Trypanosoma cruzi, Trypanosoma brucei, and Leishmania spp.) are protozoan parasites that cause neglected diseases affecting millions of people in Africa, Asia, and the Americas. In the process of infection, trypanosomatids evade and survive the immune system attack, which can lead to a chronic inflammatory state that induces cumulative damage, often killing the host in the long term. The immune mediators involved in this process are not entirely understood. Most of the research on the immunologic control of protozoan infections has been focused on acute inflammation. Nevertheless, when this process is not terminated adequately, permanent damage to the inflamed tissue may ensue. Recently, a second process, called resolution of inflammation, has been proposed to be a pivotal process in the control of parasite burden and establishment of chronic infection. Resolution of inflammation is an active process that promotes the normal function of injured or infected tissues. Several mediators are involved in this process, including eicosanoid-derived lipids, cytokines such as transforming growth factor (TGF)-β and interleukin (IL)-10, and other proteins such as Annexin-V. For example, during T. cruzi infection, pro-resolving lipids such as 15-epi-lipoxin-A4 and Resolvin D1 have been associated with a decrease in the inflammatory changes observed in experimental chronic heart disease, reducing inflammation and fibrosis, and increasing host survival. Furthermore, Resolvin D1 modulates the immune response in cells of patients with Chagas disease. In Leishmania spp. infections, pro-resolving mediators such as Annexin-V, lipoxins, and Resolvin D1 are related to the modulation of cutaneous manifestation of the disease. However, these mediators seem to have different roles in visceral or cutaneous leishmaniasis. Finally, although T. brucei infections are less well studied in terms of their relationship with inflammation, it has been found that arachidonic acid-derived lipids act as key regulators of the host immune response and parasite burden. Also, cytokines such as IL-10 and TGF-β may be related to increased infection. Knowledge about the inflammation resolution process is necessary to understand the host–parasite interplay, but it also offers an interesting opportunity to improve the current therapies, aiming to reduce the detrimental state induced by chronic protozoan infections.

Experimental therapeutic assays of Tephrosia vogelii against Leishmania major infection in murine model: in vitro and in vivo

BackgroundConventional targeted leishmanicidal chemotherapy has persistently remained prohibitive for most economically deprived communities due to costs, associated time to accessing health services and duration for successful treatment programme. Alternatives are bound to be incorporated in rational management of leishmaniasis by choice or default due to accessibility and cultural beliefs. Therefore, there is need to rigorously investigate and appraise the activity of medicinal compounds that may have anti-leishmanicidal activity especially in the context of products that are already being utilized by the populations for other ailments but have limited information on their therapeutic value and possible cytoxicity. Hence, the study examined both in vivo and in vitro response of L. major infection to Tephrosia vogelii extracts in BALB/c mice as the mouse model.MethodsA comparative study design was applied for the in vivo and in vitro assays of the extract with Pentostam (GlaxoSmithKline, UK) and Amphotericin B [Fungizone™, X-Gen Pharmaceuticals (US)] as standard drugs.ResultsIn BALB/c mice where the chemotherapeutic extract was administered intraperitoneally, there was significantly (p < 0.05) larger reduction in lesion size and optimal control of parasite burden than those treated orally. However, standard drugs showed better activity. Tephrosia vogelii had 50% inhibitory concentration (IC50) and IC90 of 12 and 68.5 μg/ml respectively, while the standard drugs had IC50 and IC90 of 5.5 and 18 μg/ml for Pentostam and 7.8 and 25.5 μg/ml for Amphotericin B in that order. In the amastigote assay, the infection rates decreased with increase in chemotherapeutic concentration. The multiplication indices for L. major amastigotes in macrophages treated with 200 µg/ml of the standard drugs and extract were significantly different (p < 0.05). 200 µg/ml of T. vogelii extract showed a multiplication index of 20.57, 5.65% for Amphotericin B and 9.56% for Pentostam. There was also significant difference (p < 0.05) in levels of Nitric oxide produced in the macrophages.ConclusionsThe findings demonstrated that T. vogelii extract has anti-leishmanial activity and further assays should be done to ascertain the active compounds responsible for anti-leishmanial activity.

IL-4Rα Signaling in Keratinocytes and Early IL-4 Production Are Dispensable for Generating a Curative T Helper 1 Response in Leishmania major-Infected C57BL/6 Mice.

Experimental infection with the protozoan parasite Leishmania major has been extensively used to understand the mechanisms involved in T helper cell differentiation. Following infection, C57BL/6 mice develop a small self-healing cutaneous lesion and they are able to control parasite burden, a process linked to the development of T helper (Th) 1 cells. The local presence of IL-12 has been reported to be critical in driving Th1 cell differentiation. In addition, the early secretion of IL-4 was reported to potentially contribute to Th1 cell differentiation. Following infection with L. major, early keratinocyte-derived IL-4 was suggested to contribute to Th1 cell differentiation. To investigate a putative autocrine role of IL-4 signaling on keratinocytes at the site of infection, we generated C57BL/6 mice deficient for IL-4Rα expression selectively in keratinocytes. Upon infection with L. major, these mice could control their inflammatory lesion and parasite load correlating with the development of Th1 effector cells. These data demonstrate that IL-4 signaling on keratinocytes does not contribute to Th1 cell differentiation. To further investigate the source of IL-4 in the skin during the first days after L. major infection, we used C57BL/6 IL-4 reporter mice allowing the visualization of IL-4 mRNA expression and protein production. These mice were infected with L. major. During the first 3 days after infection, skin IL-4 mRNA expression was observed selectively in mast cells. However, no IL-4 protein production was detectable locally. In addition, early IL-4 blockade locally had no impact on subsequent Th1 cell differentiation and control of the disease. Taken together, the present data rule out a major role for skin IL-4 and keratinocyte IL-4Rα signaling in the development of a Th1 protective immune response following experimental infection with L. major.

T1/ST2 deficient mice display protection against Leishmania infantum experimental infection

T1/ST2 is a surface marker selectively expressed on type 2 helper (TH2) effector cells. As Leishmania infection in susceptible BALB/c mice have ascribed to a polarized TH2 response, this study aim to investigate the T1/ST2 (the receptor for IL-33), as a typical TH2 marker in the postulation that a shift towards a beneficial TH1 response would occur in the absence of ST2. For this, ST2 knockout (ST2−/−) and WT BALB/c mice were experimentally infected in the retro-orbital sinus with L. infantum. We showed that ST2−/− animals displayed better control of parasite burden in both spleen and liver tissues at different time points of chronic phases, and reduced spleenomegaly and hepatomegaly compared with the wild-type (WT) mice. This was associated with increased in the IFN-γ levels and expression by CD4+ and CD8+ lymphocytes. The inflammatory response encompasses transaminases (AST and ALT) releases and NO productions were remarkably lower in ST2−/− mice compared with WT. These data suggest that, ST2−/−) exert protection against L. infantum infection and probably shift the immune response toward TH1 induction.

Type I interferon signalling suppresses anti-parasitic CD4+ T cell responses during visceral leishmaniasis

Abstract Many pathogens, including viruses, bacteria, and protozoan parasites, suppress cell mediated immune responses through activation of type I Interferon (IFN-1) signalling. However the role of IFN-1 during Leishmania donovani infection causing visceral leishmaniasis (VL) is not well known. Here we report that IFN-1 play an important role in the pathogenesis of VL by impairing parasite clearance and suppressing pro-inflammatory cytokine production. Mice lacking type-1 IFN signalling (B6.IFNαR1−/− mice) had enhanced pro-inflammatory cytokine production and better control of parasite burden in liver as well as spleen compared to wild type C57BL/6 mice. IFN-1 signalling suppressed the CD4+ derived IFN-γ production and prevented Th1 response from controlling parasite replication. Experiment using bone marrow chimeric mice revealed that IFN-1 did not suppress CD4+ T via directly acting to this cell type. Using conventional dendritic cell (cDC) specific IFN-1 deficient mice (CD11c Cre-IFNARfl/fl), we observed that IFN-1 hampered CD4+ T cells response acting via dendritic cells. Studies in VL patients supported these findings and showed enhanced accumulation of mRNA encoding type I IFN signature genes in peripheral blood mononuclear cells (PBMCs) that were reduced following successful drug therapy. Critically, we also showed, using a whole blood assay, that blockade of type-1 IFN signalling enhanced antigen specific IFN-γ production, and that this response was HLA-II restricted. Together, these results identify the type-1 IFN signalling pathways as a potential therapeutic target to treat VL by stimulating anti-parasitic CD4+ T cell responses.

Are Neutrophil Extracellular Traps Playing a Role in the Parasite Control in Active American Tegumentary Leishmaniasis Lesions?

Neutrophil extracellular traps (NETs) have been described as a network of extracellular fibers composed by DNA, histones and various proteins/enzymes. Studies have demonstrated that NETs could be responsible for the trapping and elimination of a variety of infectious agents. In order to verify the presence of NETs in American tegumentary leishmaniasis (ATL) and their relationship with the presence of amastigotes we evaluated active cutaneous lesions of 35 patients before treatment by the detection of parasites, neutrophils (neutrophil elastase) and histones through immunohistochemistry and confocal immunofluorescence. Intact neutrophils could be detected in all ATL lesions. NETs were present in 27 patients (median 1.1; range from 0.1 to 23.5/mm2) with lesion duration ranging from one to seven months. NETs were in close proximity with neutrophils (r = 0.586; p = 0.0001) and amastigotes (r = 0.710; p = 0.0001). Two patterns of NET formation were detected: small homogeneously distributed networks observed in all lesions; and large structures that could be visualized at a lower magnification in lesions presenting at least 20% of neutrophils. Lesions presenting the larger NET formation showed high parasite detection. A correlation between NET size and the number of intact amastigotes was observed (p=0.02). As we detected an association between NET and amastigotes, our results suggest that neutrophil migration and NET formation could be stimulated and maintained by stimuli derived from the parasite burden/parasite antigen in the extracellular environment. The observation of areas containing only antigens not intermingled with NETs (elastase and histone) suggests that the involvement of these structures in the control of parasite burden is a dynamic process in which the formation of NETs is exhausted with the destruction of the parasites. Since NETs were also associated with granulomas, this trapping would favor the activity of macrophages in order to control the parasite burden.

Novel dialkylphosphorylhydrazones: Synthesis, leishmanicidal evaluation and theoretical investigation of the proposed mechanism of action

As part of a program to develop new drugs for the treatment of neglected diseases, new dialkylphosphorylhydrazones were synthesized and evaluated against the trypanosomatid parasites Leishmania braziliensis and Leishmania amazonensis. The synthesis of these compounds proved satisfactory with yields ranging from moderate to good. The most active compounds against L. braziliensis presented IC50 values in the 10−2 μM range, similar to that of the reference drug pentamidine. Two compounds, 4m and 4n, showed a significant dose dependent decrease in the infection index of L. amazonensis infected macrophages and caused a complete healing of nodules and ulcers when tested in vivo against L. amazonensis-infected mice, but the control of parasite burden at the inoculation site was statistically significant only in the case of treatment with 4n. A target fishing (reverse docking) approach using molecular docking with 15 enzymes of L. braziliensis indicated that the probable target of the active compounds was hexokinase, the first enzyme of the glycolytic pathway.

A role for dectin-1 in the CNS during chronic Toxoplasma gondii infection (MPF5P.739)

Abstract The latent stage of T.gondii infection is characterized by the formation of tissue cysts within the CNS. These tissue cysts are formed by manipulation of the parasitophorous vacuole, and chitin is a structural component of the cyst wall. Our lab has shown that Toxoplasma cysts induce an M2 phenotype in macrophages in a contact-dependent manner. Upon contact, these macrophages actively secrete the mammalian chitinase, AMCase, to break down the cyst wall. We have previously demonstrated that AMCase production by macrophages is essential for control of cyst burden in the brain during T. gondii infection. The molecular interactions involved in macrophage-cyst recognition, and the signaling pathway for AMCase production are as yet unknown. Although chitin recognition has been poorly defined, studies suggest dectin-1 may be a receptor. Here, we present data on a role for dectin-1 during T. gondii infection. Dectin-1 is upregulated in the brain in response to infection and is expressed on arginase-1+, M2 macrophages. Consistent with dectin-1 expression on M2 macrophages, dectin-1 is not required to control parasite burden or induce an inflammatory immune response in vivo. However, dectin-1 deficient mice do exhibit trends towards decreased cyst numbers in the brain and a concomitant increase in AMCase transcripts and AMCase activity ex vivo. Thus, this data suggests that dectin-1 is modulating the immune response and chitinase production during chronic Toxoplasma infection.

The CD14+CD16+ Inflammatory Monocyte Subset Displays Increased Mitochondrial Activity and Effector Function During Acute Plasmodium vivax Malaria

Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria. Here, we demonstrate that P. vivax–infected patients display significant increase in circulating monocytes, which were defined as CD14+CD16− (classical), CD14+CD16+ (inflammatory), and CD14loCD16+ (patrolling) cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the CD16+ cells, in particular the CD14+CD16+ monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, CD14+ were distinguished from CD14lo monocytes by displaying larger and more active mitochondria. CD14+CD16+ monocytes were more efficient in phagocytizing P. vivax-infected reticulocytes, which induced them to produce high levels of intracellular TNF-α and reactive oxygen species. Importantly, antibodies specific for ICAM-1, PECAM-1 or LFA-1 efficiently blocked the phagocytosis of infected reticulocytes by monocytes. Hence, our results provide key information on the mechanism by which CD14+CD16+ cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection.

Preliminary phytochemical and antileishmanial studies of the ethanolic extracts of Pterodon pudescens

Pentavalent antimonials are the first choice for the treatment of human leishmaniasis. However in rural areas the traditional plants may be preferred for the treatment of lesions. In recent years a number of papers are published related to the natural products especially plant derivative with infectious diseases. The present work was undertaken to evaluate the antileishmanial activity of Pterodon pubescens which is a native tree widely distributed over the central region of Brazil and used in folk medicine as wine infusions to treat inflammatory disease. The phytochemical screening and the biological essay of ethanolic extract of Pterodon pudescens (PPE) leaves at the concentrations of 150, 300, 450, 600 µg/ml were tested in vitro in Leishmania amazonensis-infected macrophages to support its traditional medicinal use as a leishmaniasis remedy. Phytochemical screening of PPE has shown the presence of catechemical tannins, steroids, triterpenoids and flavonoids. The biological test suggests that PPE were found to control parasite burden of cell cultures in dose-dependent manner. These findings highlight the fact that the apparent potency of Pterodon pudescens compounds, together with their widely distribution over Latin America and Brazil, may represent a promising antileishmanial agent.

MiR-146a and miR-155 Delineate a MicroRNA Fingerprint Associated with Toxoplasma Persistence in the Host Brain

microRNAs were recently found to be regulators of the host response to infection by apicomplexan parasites. In this study, we identified two immunomodulatory microRNAs, miR-146a and miR-155, that were coinduced in the brains of mice challenged with Toxoplasma in a strain-specific manner. These microRNAs define a characteristic fingerprint for infection by type II strains, which are the most prevalent cause of human toxoplasmosis in Europe and North America. Using forward genetics, we showed that strain-specific differences in miR-146a modulation were in part mediated by the rhoptry kinase, ROP16. Remarkably, we found that miR-146a deficiency led to better control of parasite burden in the gut and most likely of early parasite dissemination in the brain tissue, resulting in the long-term survival of mice.

Serum-Mediated Activation of Macrophages Reflects TcVac2 Vaccine Efficacy against Chagas Disease

Chagas disease is endemic in Latin America and an emerging infectious disease in the United States. No effective treatments are available. The TcG1, TcG2, and TcG4 antigens are highly conserved in clinically relevant Trypanosoma cruzi isolates and are recognized by B and T cells in infected hosts. Delivery of these antigens as a DNA prime/protein boost vaccine (TcVac2) elicited lytic antibodies and type 1 CD8(+) T cells that expanded upon challenge infection and provided >90% control of parasite burden and myocarditis in chagasic mice. Here we determined if peripheral blood can be utilized to capture the TcVac2-induced protection from Chagas disease. We evaluated the serum levels of T. cruzi kinetoplast DNA (TckDNA), T. cruzi 18S ribosomal DNA (Tc18SrDNA), and murine mitochondrial DNA (mtDNA) as indicators of parasite persistence and tissue damage and monitored the effect of sera on macrophage phenotype. Circulating TckDNA/Tc18SrDNA and mtDNA were decreased by >3- to 5-fold and 2-fold, respectively, in vaccinated infected mice compared to nonvaccinated infected mice. Macrophages incubated with sera from vaccinated infected mice exhibited M2 surface markers (CD16, CD32, CD200, and CD206), moderate proliferation, a low oxidative/nitrosative burst, and a regulatory/anti-inflammatory cytokine response (interleukin-4 [IL-4] plus IL-10 > tumor necrosis factor alpha [TNF-α]). In comparison, macrophages incubated with sera from nonvaccinated infected mice exhibited M1 surface markers, vigorous proliferation, a substantial oxidative/nitrosative burst, and a proinflammatory cytokine response (TNF-α ≫ IL-4 plus IL-10). Cardiac infiltration of macrophages and TNF-α and oxidant levels were significantly reduced in TcVac2-immunized chagasic mice. We conclude that circulating TcDNA and mtDNA levels and macrophage phenotype mediated by serum constituents reflect in vivo levels of parasite persistence, tissue damage, and inflammatory/anti-inflammatory state and have potential utility in evaluating disease severity and efficacy of vaccines and drug therapies.

The role of LIGHT a member of the TNFSF in regulation of secondary immunity to Leishmania major (P3344)

Abstract We previously showed that LIGHT, (lymphotoxin like, exhibits inducible expression and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes) and its receptors are critically important for initiation of CD4+ T helper (Th1) cell response and development of primary immunity to Leishmania major infection in mice. Here, we further characterized the contributions of this molecule in the activation of dendritic cells (DCs), L. major-induced IL-12 production and secondary anti-Leishmania immunity. We show that blockade of LIGHT significantly impaired DC maturation and expression of costimulatory molecules including, CD40 and CD86. In addition, blockade of LIGHT signaling lead to impairment in L. major-induced IL-12p40 production by DCs in vivo and a concomitant reduction in the number of cells recruited into the draining lymph nodes as well as early IFN-γ production by CD4+ T cells following L. major infection. Furthermore, we show that LIGHT is required at both priming and maintenance stages of anti-Leishmania immunity. Interestingly, blockade of LIGHT had no effect on delayed-type hypersensitivity (DTH) response and control of parasite burden following secondary L. major challenge. Collectively, these results show that LIGHT is critical for IL-12 production by DCs and subsequent priming and maintenance of IFN-γ response by CD4+ T cells during primary but is dispensable during secondary anti-Leishmania immunity.

The immunology and genetics of resistance of sheep to Teladorsagia circumcincta

Teladorsagia circumcincta is one of the most economically important gastrointestinal nematode parasites of sheep in cool temperate regions, to which sheep show genetically-varying resistance to infection. This is a very common parasite and viable sheep production requires the extensive use of anthelmintic drugs. However, the emergence of drug-resistant parasites has stimulated the search for alternative control strategies to curb production losses. Lambs become infected soon after weaning and begin to control parasite burden within 8-10 weeks of continual infection. This control is an acquired characteristic mediated by the development of parasite-specific antibodies. This paper describes the immunology associated with resistance and susceptibility, focussing on differential T cell activation that regulates the production of specific effector mechanisms. It continues by summarizing the methods used to identify genes that could be exploited as molecular markers of selection for resistance. In particular it focusses on the link between understanding the molecular immunology of infection and the identification of candidate genes for selection.

Canine Angiostrongylosis in Naturally Infected Dogs: Clinical Approach and Monitoring of Infection after Treatment

Canine angiostrongylosis is an increasingly reported disease in Europe which can be fatal if left untreated. The wide range of clinical presentation along with the absence of pathognomonic alterations can make the diagnosis challenging; thus any additional information that may provide clues to an early diagnosis may be of value, in order to ensure adequate anthelmintic treatment. Aim of the study was to assess a clinicopathological scoring system associated with natural Angiostrongylus vasorum infection diagnosed in canine patients during clinical practice, to clinically and paraclinically monitor infected dogs after treatment, and to monitor the presence of L1 larvae in faecal samples by Baermann's test. Of the total 210 enrolled animals A. vasorum infection was diagnosed in 7 dogs. These dogs were clinically and paraclinically investigated and monitored after specific treatment. Further 3 symptomatic dogs were retrospectively included in the monitoring. Results suggest that the computed scoring system can help to increase the clinical suspicion of infection particularly in asymptomatic dogs before the onset of potentially lethal lesions. Data of faecal monitoring suggested that treatment may control parasite burden but be unable to eradicate infection. Thus, a continued faecal monitoring after treatment is advisable for identification of still infected or reinfected dogs.