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Summary: Group 2 innate lymphoid cells (ILC2s) play critical roles in the induction of type 2 inflammation, response to parasite infection, metabolic homeostasis, and tissue repair. These multifunctional roles of ILC2s are tightly controlled by complex regulatory systems in the local microenvironment, the disruption of which may cause various health problems. This review summarizes up‐to‐date knowledge regarding positive and negative regulators for ILC2s based on their function and signaling pathways, including activating cytokines (IL‐33, IL‐25; MAPK, NF‐κB pathways), co‐stimulatory cytokines (IL‐2, IL‐7, IL‐9, TSLP; STAT5, IL‐4; STAT6, TNF superfamily; MAPK, NF‐κB pathways), suppressive cytokines (type1 IFNs, IFN‐γ, IL‐27; STAT1, IL‐10, TGF‐β), transdifferentiation cytokines (IL‐12; STAT4, IL‐1β, IL‐18), lipid mediators (LTC4, LTD4, LTE4, PGD2; Ca2+‐NFAT pathways, PGE2, PGI2; AC/cAMP/PKA pathways, LXA4, LTB4), neuropeptides (NMU; Ca2+‐NFAT, MAPK pathways, VIP, CGRP, catecholamine, acetylcholine), sex hormones (androgen, estrogen), nutrients (butyrate; HDAC inhibitors, vitamins), and cell‐to‐cell interactions (ICOSL‐ICOS; STAT5, B7‐H6‐NKp30, E‐cadherin‐KLRG1). This comprehensive review affords a better understanding of the regulatory network system for ILC2s, providing impetus to develop new treatment strategies for ILC2‐related health problems. [ABSTRACT FROM AUTHOR]

Parasites remain one of the most important causes of morbidity and mortality in the tropical landscape. Of these, granulomatous amoebic encephalitis (GAE), leishmaniasis and malaria are 3 common parasitic diseases which can be fatal if left untreated. The available drugs seem to be ineffective as resistant strains have emerged in recent years. It is timely for medicinal plants have been given much attention as an alternative for the available chemotherapeutic drugs. This review was conducted to evaluate the anti-parasitic effects of medicinal plants from different parts of the world. It was found that large numbers of plants showed strong anti-parasitic potential; Clerodendrum rotundifolium Oliv. leaves water fraction, Clerodendrum rotundifolium Oliv. leaves methanol fraction and Microglossa pyrifolia showed strong anti-malarial activity with IC50 of 0.01, 0.02 and 0.05 μg/ml in vitro. Limouni olive is a strong amoebicidal agent with IC50 of 5.11 μg/ml. Ethanol extracts from H. stignocarpa leaves (4.69 μg/ml), J. cuspidifolia leaves (10.96 μg/ml) and Jacaranda caroba leaves (13.22 μg/ml) showed strong activity against Leishmania spp. with IC50 values lower than 25 μg/ml. In conclusion, these promising results suggest that future research on medicinal plants needs to be done to identify its active constituents, cytotoxicity, effectivity and feasibility to be utilized against infections caused by these parasites. Furthermore, phytochemical investigations should be undertaken to achieve the effectiveness of therapeutic agents particularly in limited resource settings. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis (CL) is an immune-mediated skin pathology caused mainly by Leishmania (L.) major, Leishmania tropica, Leishmania braziliensis, L. mexicana, and L. amazonensis. The burden of CL in terms of morbidity and social stigmas are concentrated on certain developing countries in Asia, Africa, and South America. People with asymptomatic CL represent a large proportion of the infected individuals in the endemic areas who exhibit no lesion and can control the infection by as yet not fully understood mechanisms. Currently, there is no approved prophylactic control measure for CL. Discovery of biomarkers of CL infection and immunity can inform the development of more precise diagnostics tools as well as curative or preventive strategies to control CL. Herein, we provide a brief overview of the state-of-the-art for the biomarkers of CL with a special emphasis on the asymptomatic CL biomarkers. Among the identified CL biomarkers so far, direct biomarkers which indicate the actual presence of the infection as well as indirect biomarkers which reflect the host's reaction to the infection, such as alterations in delayed type hypersensitivity, T-cell subpopulations and cytokines, adenosine deaminase, and antibodies against the sand fly saliva proteins are discussed in detail. The future avenues such as the use of systems analysis to identify and characterize novel CL biomarkers are also discussed. [ABSTRACT FROM AUTHOR]

Immunosuppression in sepsis reduces both αβ and γδ T cell subsets. Anisakis sp. is a parasitic nematode with a high prevalence in Spain. Previous contact with the parasite is related to a decrease in γδ T cells. Anti- Anisakis antibodies were measured and related to αβ and γδ T cells in 114 septic patients versus 97 healthy controls. Significant differences were seen with respect to the groups with severe sepsis and septic shock where lower anti- Anisakis levels were observed. A similar decrease appeared in the case of specific IgM with significant differences between the groups of control/uncomplicated sepsis versus severe sepsis and septic shock. These differences were also apparent in the case of specific IgA. The lowest IgE levels were detected in the septic shock group. Anti- Anisakis IgG levels significantly increased in septic shock groups compared with the controls. We observed positive correlations among anti- Anisakis IgA levels and all γδ T cell subsets. There were negative correlations among IgA levels and APACHE and SOFA indices. Greater contact with the parasite (IgG) was directly related with septic shock, inflammation and markers of sepsis severity. A lack of protection in the mucosa (IgA and γδ T cells) was associated with the disease severity. [ABSTRACT FROM AUTHOR]

All Theileria parasites have definitive natural hosts that act as carriers. Incidental infections of uncommon hosts do occur raising questions regarding host specificity and its drivers. Reported hosts for Theileria taurotragi include bushbuck, cattle and eland. More recently T. taurotragi was detected in African buffalo, which may have implications for accurate diagnostics of T. parva . The current study therefore investigated the host specificity of T. taurotragi by developing a specific and sensitive real-time Taqman PCR assay. Animals were screened from areas where Rhipicephalus appendiculatus , the tick vector for both T. parva and T. taurotragi was present. While T. taurotragi was detected in cattle, eland, kudu and nyala, African buffalo (n = 352) was negative. Conversely, these same buffalo showed a prevalence of 72–100% for T. parva . While transmission of T. taurotragi to cattle was successful using the same infected tick batch, transmission to African buffalo did not occur. The results suggest that African buffalo is not a natural host of T. taurotragi and would probably not harbor anti-schizont antibodies against T. taurotragi . This would preclude T. taurotragi as possible source of cross-reactivity in the T. parva immunofluorescent antibody test. Host specificity of T. taurotragi for members of the Tragelaphini, but not buffalo also suggests that host specificity may have been an important driver in the speciation of the T. taurotragi clade. Different scenarios for co-evolution of host and parasite are discussed with implications for time of divergence for this Theileria clade. [ABSTRACT FROM AUTHOR]

The immunoneuroendocrine network interactions between prolactin (PRL) and the immune system are important because PRL modulates humoral and cellular immune responses in both physiological and pathological situations, as it occurs in parasitic diseases. Protozoa parasites such as Leishmania sp, Toxopasma gondii, Trypanosoma cruzi or Plasmodium falciparum induce inflammation and raise the release of pro-inflammatory cytokines. PRL triggers anti-parasitic activities, in cells of the immune system at multiple levels, either increasing NK cytolytic activities or enhancing phagocytosis and T helper cytokines 1 (Th1) immune responses. On the contrary, PRL also may promote infections caused by helminthic parasites such as Toxocara canis, or Taenia solium, these parasites possess PRL receptors and could use PRL to increase their growth, movement or reproduction. [ABSTRACT FROM AUTHOR]

Mansonellosis is an endemic disease in the South and Central America. In Brazil, one of the etiological agents is Mansonella ozzardi . This filarial infection is yet poorly understood, with a controversial morbity, presenting since a oligosymptoms, malaria-like signs or without complaint in humans. The knowledge of the human immune response to microfilariae infection is limited mainly by different evolutionary cycles of the parasite in the host. In addition, the prevalence of this filarial parasite infection is high in several regions of Amazonas State. A cross-sectional study was conducted in an endemic area for microfilariae of M. ozzardi (MF) infection in the Amazonas State, Brazil. Proinflammatory and regulatory cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-gamma, and IL-17A) were measured in cryopreserved serum using the Cytometric Bead Array techniques (CBA) in 54 patients diagnosed with M. ozzardi infection and 55 individuals without the infection were included in the study (Controls). The IL-4, IL-6 and IL-10 level increased in infected patients with MF infection, while IL-17A increased in control only. When we compared controls to patients with high or low parasite load, the increased level of IL-6 and IL-10 were maintained. IL-6 contributes to the proinflammatory activity and IL-10 modulates Th1, Th2 and Th17 immune response. Furthermore, IL-4 was detected as a marker in the MF infection and MF patients with low parasite load, indicating the action of the Th2 cell response. The complex network of cytokines acting during M. ozzardi infection depends on a fine balance to determine a host protective effect or filarial persistence. Therefore, these results suggest that the immune response in MF infection is modulated by IL-6/IL-10 axis. [ABSTRACT FROM AUTHOR]

Summary: Toxoplasma gondii is a protozoan parasite capable of invading immune cells and co‐opting their migratory pathways to disseminate through the host. Natural Killer (NK) cells can be directly invaded by the parasite and this invasion alters NK cell migration, producing a hypermotile phenotype. However, the consequences of this hypermotile phenotype for the dissemination of T. gondii to the brain remain unknown. To address this, C57BL6/J mice were infected with freshly egressed tachyzoites (type IIPrugniaud strain) or with parasitized NK cells. Under both conditions, parasite loads in the brain were comparable, indicating that parasitized NK cells were not able to facilitate spread of T. gondii to the brain. Consistent with this, we found no evidence for the recruitment of endogenous NK cells to the brain at early time points post‐infection, nor any changes in the expression of α4β1 integrin, involved in recruitment of NK cells to the brain. We therefore found no evidence for a role for hypermotile NK cells in delivery of parasites to the brain during acute infection with T. gondii. [ABSTRACT FROM AUTHOR]

Summary: This study investigated the local immune response at larval attachment sites in Santa Gertrudis cattle with low and high levels of tick resistance. Skin samples with tick larvae attached were collected from Santa Gertrudis cattle at the end of a period of 25 weekly infestations, when the animals manifested highly divergent tick‐resistant phenotypes. There was a tendency for more CD3+, CD4+, CD8+, CD25+, γδ T cells and neutrophils to concentrate at larval tick attachment site in susceptible cattle than in resistant cattle but the differences were significant only for γδ T cells and CD4+ cells. Most of the cattle developed intra‐epidermal vesicles at the larval attachment site but the predominant cell within or around the vesicles was the neutrophil in susceptible animals and eosinophil in the resistant animals. The monoclonal antibodies (mAbs) specific for CD45 and CD45 RO antigens reacted with skin leucocytes from a higher number of susceptible cattle than resistant cattle. Our data suggest that some of the cellular responses mounted at larval attachment site are not involved in tick protection. The mAbs specific for CD45 and CD45 RO directly, or a test for CD45 genotype might be developed as markers of tick susceptibility or resistance. [ABSTRACT FROM AUTHOR]

Summary: Manipulation of costimulatory and surface molecules that shape the extent of immune responses by Leishmania is suggested as one of the mechanisms of evading the host's defences. The experiments reported here were designed to evaluate the expressions of CD11b, CD11c, CD14, CD18, CD54, CD80, CD86, CD206, MHC class II and TLR‐2 (Toll‐like receptor 2) in human macrophages infected with L. amazonensis. Phenotypic evaluation revealed a negative modulation in CD11b, CD11c, CD14, CD18, CD54 and MHC class II molecules, depending on the level of infection. The results showed that as early as 1 hour after infection no reduction in marker expression occurs, whereas after 24 hours, downregulation of these molecules was observed in macrophages. No significant changes were observed in the expressions of CD80, CD86, CD206 and TLR2. Evidence of the differential modulation of markers expression and that after parasite uptake no reduction in surface marker expression occurs indicates that parasite internalization is not involved in the phenomena of down‐modulation. [ABSTRACT FROM AUTHOR]

Summary: Gastrointestinal (GI) nematodes are a group of successful multicellular parasites that have evolved to coexist within the intestinal niche of multiple species. It is estimated that over 10% of the world's population are chronically infected by GI nematodes, making this group of parasitic nematodes a major burden to global health. Despite the large number of affected individuals, there are few effective treatments to eradicate these infections. Research into GI nematode infections has primarily focused on defining the immunological and pathological consequences on host protection. One important but neglected aspect of host protection is mucus, and the concept that mucus is just a simple barrier is no longer tenable. In fact, mucus is a highly regulated and dynamic‐secreted matrix, underpinned by a physical hydrated network of highly glycosylated mucins, which is increasingly recognized to have a key protective role against GI nematode infections. Unravelling the complex interplay between mucins, the underlying epithelium and immune cells during infection are a major challenge and are required to fully define the protective role of the mucus barrier. This review summarizes the current state of knowledge on mucins and the mucus barrier during GI nematode infections, with particular focus on murine models of infection. [ABSTRACT FROM AUTHOR]

Toxocara canis is the helminth causing Toxocariasis, a parasitic disease with medical and veterinary implications. Their final host are members of the family Canidae and as paratenic hosts, most of the mammals are sensitive (man, rat, mouse, among others). It has been reported that a pituitary hormone, prolactin, it is responsible for reactivation and migration of larvae to the uterus and mammary gland during the last third of gestation in bitches. In addition, this hormone has been shown to play an important role in the regulation of the immune response. Thus, the aim of this study, was to evaluate the effect of hypophysectomy in the rat model of Toxocariasis, on the immune response against this parasite during a chronic infection, for which parasite loads were analyzed in different organs (lung and brain). Furthermore, serum specific antibody titers, and percentages of different cells of the immune system were also determined. The results showed a decrease in the number of larvae recovered from lung and brain in the hypophysectomized animals. In this same group of animals, there was no production of specific antibodies against the parasite. As for the percentages of the cells of the immune system, there are differences in some subpopulations due to surgery and others due to infection. Our results demonstrated that the lack of pituitary hormones alters parasite loads and the immune response to the helminth parasite Toxocara canis . [ABSTRACT FROM AUTHOR]

C C chemokine receptor type 5 (CCR5) is a chemokine receptor that influences the immune response to infectious and parasitic diseases. This study aimed to determine whether the CCR5Δ32 and CCR5 59029 A/G polymorphisms are associated with the development of ocular toxoplasmosis in humans. Patients with positive serology for Toxoplasma gondii were analyzed and grouped as ‘with ocular toxoplasmosis’ (G1: n = 160) or ‘without ocular toxoplasmosis’ (G2: n = 160). A control group (G3) consisted of 160 individuals with negative serology. The characterization of the CCR5Δ32 and CCR5 59029 A/G polymorphisms was by PCR and by PCR-RFLP, respectively. The difference between the groups with respect to the mean age (G1: mean age: 47.3, SD ± 19.3, median: 46 [range: 18–95]; G2: mean age: 61.3, SD ± 13.7, median: 61 [range: 21–87]; G3: mean age: 38.8, SD ± 17.9, median: 34 [range: 18–80]) was statistically significant (G1 vs.G2: p-value <0.0001; t = 7.21; DF = 318; G1 vs.G3: p-value <0.0001; t = 4.32; DF = 318; G2 vs. G3: p-value <0.0001; t = 9.62; DF = 318). The Nagelkerke r 2 value was 0.040. There were statistically significant differences for the CCR5/CCR5 (p-value = 0.008; OR = 0.261), AA (p-value = 0.007; OR = 2.974) and AG genotypes (p-value = 0.018; OR = 2.447) between G1 and G2. Individuals with the CCR5/CCR5 genotype and simultaneously the CCR5-59029 AA or AG genotypes have a greater risk of developing ocular toxoplasmosis (4% greater), which may be associated with a strong and persistent inflammatory response in ocular tissue. [ABSTRACT FROM AUTHOR]

As we describe the immune system in ever more exquisite detail, we might find that no matter how successful, this approach will not be sufficient to understand the spread of infectious agents, their susceptibility to vaccine therapy, and human disease resistance. Compared with the strict reductionism practiced as a means of characterizing most biological processes, I propose that the progression and outcome of disease-causing host–parasite interactions will be more clearly understood through a focus on disease ecology. [ABSTRACT FROM AUTHOR]

Protozoan parasites such as Plasmodium spp., Leishmania spp., Trypanosoma spp., and Toxoplasma gondii are major causes of parasitic diseases in both humans and animals. The immune system plays a critical role against protozoa, but their immune mechanism remains poorly understood. This highlights the need to investigate the function of immune cells involved in the process of parasite infections and the responses of host immune system to parasite infections. Mast cells (MCs) are known to be central players in allergy and anaphylaxis, and it has been demonstrated that MCs have crucial roles in host defense against a number of different pathogens, including parasites. To date, there are many studies that have examined the interaction of helminth-derived antigens and MCs. As one of the major effector cells, MCs also play an important role in the immune response against some parasitic protozoa, but their role in protozoan infections is, however, less well characterized. Herein, we review the current knowledge about the roles of MCs and their mediators during infections involving highly pathogenic protozoa including Plasmodium spp., Leishmania spp., Trypanosoma spp., and T. gondii. We offer a general review of the data from patients and experimental animal models infected with the aforementioned protozoa, which correlate MCs and MC-derived mediators with exacerbated inflammation and disease progression as well as protection against the parasitic infections in different circumstances. This review updates our current understanding of the roles of MCs during parasitic protozoan infections, and the participation of MCs in parasitic protozoan infections could be of a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Cystic echinococcosis ( CE) caused by the cestode Echinococcus granulosus ( E. granulosus) is a zoonotic parasitic disease. The effective immune evasion mechanisms of E. granulosus allow it to parasitize its hosts. However, the status of the innate and adaptive immune cells and their contributions to E. granulosus progression remain poorly understood. In this study, we aimed to determine the impact of E. granulosus infection on T cells, NK cell responses and TGF-β expression during the early infection phase in BALB/c mice. In E. granulosus infections, there was an increasing tendency in the percentage of CD4+ CD25+ T cells and CD4+Foxp3+ T cells and peripheral blood TGF-β levels and relative expression of the Foxp3 gene. Moreover, there were a decreasing tendency in the percentage of NK cells and NK cell cytotoxicity and the expression of NKG2D on NK cells. The TGF-β1/Smad pathway was activated by E. granulosus in mice. Above results can be reversed by the inhibitor SB-525334 (potent activin receptor-like kinase 5 inhibitor). These results suggest that the TGF-β/Smad pathway plays an important role in changes of T-cell or NK cell responses. These results may contribute to revealing the preliminary molecular mechanisms in establishing hydatid infection. [ABSTRACT FROM AUTHOR]

Nod-like receptors (NLRs) have gained attention in recent years because of the ability of some family members to assemble into a multimeric protein complex known as the inflammasome. The role of NLRs and the inflammasome in regulating innate immunity against bacterial pathogens has been well studied. However, recent studies show that NLRs and inflammasomes also play a role during infections caused by protozoan parasites, which pose a significant global health burden. Herein, we review the diseases caused by the most common protozoan parasites in the world and discuss the roles of NLRs and inflammasomes in host immunity against these parasites. [ABSTRACT FROM AUTHOR]

Invariant natural killer T (iNKT) cells are unique subset of innate-like T cells recognizing glycolipids. iNKT cells can rapidly produce copious amounts of cytokines upon antigen stimulation and exert potent immunomodulatory activities for a wide variety of immune responses and diseases. We have revealed the regulatory effect of iNKT cells on autoimmunity with a serial of publications. On the other hand, the role of iNKT cells in parasitic infections, especially in recently attractive topic "hygiene hypothesis," has not been clearly defined yet. Bacterial and parasitic cell wall is a cellular structure highly enriched in a variety of glycolipids and lipoproteins, some of which may serve as natural ligands of iNKT cells. In this review, we mainly summarized the recent findings on the roles and underlying mechanisms of iNKT cells in parasite infections and their cross-talk with Th1, Th2, Th17, Treg, and innate lymphoid cells. In most cases, iNKT cells exert regulatory or direct cytotoxic roles to protect hosts against parasite infections. We put particular emphasis as well on the identification of the natural ligands from parasites and the involvement of iNKT cells in the hygiene hypothesis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to monitor abundance and activation of local CD8β-expressing T-cell populations during Eimeria tenella infections of naïve chickens and chickens immune by previous infections. Chickens were infected with E. tenella up to three times. Caecal T-cell receptor ( TCR) γ/δ- CD8β+ cells (cytotoxic T lymphocytes; CTL) and TCRγ/δ+ CD8β+ cells were characterized with respect to activation markers (blast transformation, CD25 and cell surface CD107a). Cells were also induced to degranulate in vitro as a measure of activation potential. Major findings included a prominent long-lasting, up to 6 weeks, increase in the proportion of CTL among caecal CD45+ cells in the later stages after primary E. tenella infection. These CTL also showed clear signs of activation, that is blast transformation and increased in vitro induced degranulation. At second and third E. tenella infection, chickens showed strong protective immunity but discrete signs of cellular activation were observed, for example increased in vitro induced degranulation of CTL. Thus, primary E. tenella infection induced clear recruitment and activation of local CTL. Upon subsequent infections of strongly immune chickens cellular changes were less prominent, possibly due to lower overall numbers of cells being activated because of the severe restriction of parasite replication. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are released by cells and contain a complex mixture of proteins, genetic information and lipids. EVs mediate cell:cell communication by transferring their molecular cargo between cells. EVs, initially discovered in mammalian systems, have been demonstrated to play critical role in immunology and cancer biology. More recently, EVs have been identified in a broad range of both unicellular and multicellular parasites. In this review we focus on the emerging roles for EVs in parasitic infections. Parasite-derived EVs can transfer virulence factors and drug-resistance markers, modify host cell gene expression and promote parasite adherence and host cell proliferation. EVs can also suppress or stimulate host immune responses. Thus, EVs are likely important in determining the outcome of parasitic infections. [ABSTRACT FROM AUTHOR]

The profile of global health today presents a striking reciprocal distribution between parasitic diseases in many of the world's lower-income countries, and ever-increasing levels of inflammatory disorders such as allergy, autoimmunity and inflammatory bowel diseases in the more affluent societies. Attention is particularly focused on helminth worm parasites, which are associated with protection from allergy and inflammation in both epidemiologic and laboratory settings. One mechanistic explanation of this is that helminths drive the regulatory arm of the immune system, abrogating the ability of the host to expel the parasites, while also dampening reactivity to many bystander specificities. Interest has therefore heightened into whether helminth parasites, or their products, hold therapeutic potential for immunologic disorders of the developed world. In this narrative review, progress across a range of trials is discussed, together with prospects for isolating individual molecular mediators from helminths that may offer defined new therapies for inflammatory conditions. [ABSTRACT FROM AUTHOR]

Summary Exposure to a plethora of environmental challenges commonly triggers pathological type 2 cell-mediated inflammation. Here we report the pathological role of the Wnt antagonist Dickkopf-1 (Dkk-1) upon allergen challenge or non-healing parasitic infection. The increased circulating amounts of Dkk-1 polarized T cells to T helper 2 (Th2) cells, stimulating a marked simultaneous induction of the transcription factors c-Maf and Gata-3, mediated by the kinases p38 MAPK and SGK-1, resulting in Th2 cell cytokine production. Circulating Dkk-1 was primarily from platelets, and the increase of Dkk-1 resulted in formation of leukocyte-platelet aggregates (LPA) that facilitated leukocyte infiltration to the affected tissue. Functional inhibition of Dkk-1 impaired Th2 cell cytokine production and leukocyte infiltration, protecting mice from house dust mite (HDM)-induced asthma or Leishmania major infection. These results highlight that Dkk-1 from thrombocytes is an important regulator of leukocyte infiltration and polarization of immune responses in pathological type 2 cell-mediated inflammation. [ABSTRACT FROM AUTHOR]

Chagas disease is caused by the protozoan Trypanosoma cruzi. The parasite reaches the secondary lymphoid organs, the heart, skeletal muscles, neurons in the intestine and esophagus among other tissues. The disease is characterized by mega syndromes, which may affect the esophagus, the colon and the heart, in about 30% of infected people. The clinical manifestations associated with T. cruzi infection during the chronic phase of the disease are dependent on complex interactions between the parasite and the host tissues, particularly the lymphoid system that may either result in a balanced relationship with no disease or in an unbalanced relationship that follows an inflammatory response to parasite antigens and associated tissues in some of the host organs and/or by an autoimmune response to host antigens. This review discusses the findings that support the notion of an integrated immune response, considering the innate and adaptive arms of the immune system in the control of parasite numbers and also the mechanisms proposed to regulate the immune response in order to tolerate the remaining parasite load, during the chronic phase of infection. This knowledge is fundamental to the understanding of the disease progression and is essential for the development of novel therapies and vaccine strategies. [ABSTRACT FROM AUTHOR]

Activation of macrophages is a key step in the initiation of immune responses, but the transcriptional mechanisms governing macrophage activation during infection are not fully understood. It was recently shown that the AP-1 family transcription factor JUNB positively regulates macrophage activation in response to Toll-like receptor agonists that promote classical or M1 polarization, as well as to the cytokine interleukin-4 ( IL-4), which elicits an alternatively activated or M2 phenotype. However, a role for JUNB in macrophage activation has never been demonstrated in vivo. Here, to dissect the role of JUNB in macrophage activation in a physiological setting, mice lacking JUNB specifically in myeloid cells were tested in two infection models: experimental cerebral malaria, which elicits a pathological type 1 immune response, and helminth infection, in which type 2 responses are protective. Myeloid-restricted deletion of Junb reduced type 1 immune activation, which was associated with reduced cerebral pathology and improved survival during infection with Plasmodium berghei. Myeloid JUNB deficiency also compromised type 2 activation during infection with the hookworm Nippostrongylus brasiliensis, leading to diminished cytokine production and eosinophil recruitment and increased parasite burden. These results demonstrate that JUNB in myeloid cells shapes host responses and outcomes during type 1 and type 2 infections. [ABSTRACT FROM AUTHOR]

Functional impairment of dendritic cells ( DCs) is part of a survival strategy evolved by Leishmania and Plasmodium parasites to evade host immune responses. Here, the effects of co-exposing human monocyte-derived DCs to Leishmania donovani promastigotes and Plasmodium falciparum-infected erythrocytes were investigated. Co-stimulation resulted in a dual, dose-dependent effect on DC differentiation which ranged from semi-mature cells, secreting low interleukin(-12p70 levels to a complete lack of phenotypic maturation in the presence of high parasite amounts. The effect was mainly triggered by the Leishmania parasites, as illustrated by their ability to induce semi-mature, interleukin-10-producing DCs, that poorly responded to lipopolysaccharide stimulation. Conversely, P. falciparum blood-stage forms failed to activate DCs and only slightly interfered with lipopolysaccharide effects. Stimulation with high L. donovani concentrations triggered phosphatidylserine translocation, whose onset presented after initiating the maturation impairment process. When added in combination, the two parasites could co-localize in the same DCs, confirming that the leading effects of Leishmania over Plasmodium may not be due to mutual exclusion. Altogether, these results suggest that in the presence of visceral leishmaniasis-malaria co-infections, Leishmania-driven effects may overrule the more silent response elicited by P. falciparum, shaping host immunity towards a regulatory pattern and possibly delaying disease resolution. [ABSTRACT FROM AUTHOR]

Background. Leishmaniasis is caused by parasites transmitted to the vertebrate host by infected sand flies. During transmission, the vertebrate host is also inoculated with sand fly saliva, which exerts powerful immunomodulatory effects on the host's immune response. Methods. We conducted a prospective cohort analysis to characterize the human immune response to Lutzomyia intermedia saliva in 264 individuals, from an area for cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. Results. Antibodies were found in 150 individuals (56.8%); immunoglobulin G1 and G4 were the predominant subclasses. Recall responses to salivary gland sonicate showed elevated production of interleukin 10 (IL-10), interleukin 13, interferon γ, CXCL9, and CCL2 compared with controls. CD4+CD25+ T cells, including Foxp3+ cells, were the main source of IL-10. L. braziliensis replication was increased (P < .05) in macrophages cocultured with saliva-stimulated lymphocytes from exposed individuals and addition of anti-IL-10 reverted this effect. Positive correlation between antibody response to saliva and cellular response to Leishmania was not found. Importantly, individuals seropositive to saliva are 2.1 times more likely to develop CL (relative risk, 2.1; 95% confidence interval, 1.07-4.2; P < .05). Conclusions. Exposure to L. intermedia sand flies skews the human immune response, facilitating L. braziliensis survival in vitro, and increases the risk of developing CL. [ABSTRACT FROM AUTHOR]

Common carp thrombocytes account for 30–40% of peripheral blood leukocytes and are abundant in the healthy animals' spleen, the thrombopoietic organ. We show that, ex vivo , thrombocytes from healthy carp express a large number of immune-relevant genes, among which several cytokines and Toll-like receptors, clearly pointing at immune functions of carp thrombocytes. Few studies have described the role of fish thrombocytes during infection. Carp are natural host to two different but related protozoan parasites, Trypanoplasma borreli and Trypanosoma carassii , which reside in the blood and tissue fluids. We used the two parasites to undertake controlled studies on the role of fish thrombocytes during these infections. In vivo , but only during infection with T. borreli , thrombocytes were massively depleted from the blood and spleen leading to severe thrombocytopenia. Ex vivo , addition of nitric oxide induced a clear and rapid apoptosis of thrombocytes from healthy carp, supporting a role for nitric oxide-mediated control of immune-relevant thrombocytes during infection with T. borreli . The potential advantage for parasites to selectively deplete the host of thrombocytes via nitric oxide-induced apoptosis is discussed. [ABSTRACT FROM AUTHOR]

Environmental factors impairing physiological condition of organisms are assumed to predispose them to parasite infections. This is because host immune function is typically condition-dependent. However, poor physiological condition has been reported to reduce host susceptibility to parasites in various systems., We examined whether such an effect can be due to altered exposure of hosts to active parasite transmission stages by investigating chemo-orientation of free-swimming cercariae larvae of a parasite Echinoparyphium aconiatum towards its snail host Lymnaea stagnalis., We used both long-term and short-term feeding treatments to manipulate the body condition and physiological traits related to food processing in experimental (i.e. target) snails and measured the preference of cercariae towards snail-conditioned water ( SCW) over clean water., We found that chemo-orientation of cercariae depended on the nutritional status of target snails. High physiological condition (long-term feeding) attracted parasites, but cercariae did not show preference towards SCW from individuals in poor physiological condition (long-term starvation). Food processing (short-term feeding treatments) did not affect chemo-orientation., Our results suggest that host condition-dependent chemo-orientation of parasite larvae is a likely mechanism explaining the reduced susceptibility of snails to infection due to food limitation in our study system. In general, the use of condition-dependent host cues can be highly beneficial for parasites as it increases their transmission to high-quality hosts. Furthermore, evolving counter adaptations to such a transmission strategy can be very difficult for hosts. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is a highly successful parasite that can manipulate host immune responses to optimize its persistence and spread. As a result, a highly complex relationship exists between T. gondii and the immune system of the host. Advances in imaging techniques, and in particular, the application of two-photon microscopy to mouse infection models, have made it possible to directly visualize interactions between parasites and the host immune system as they occur in living tissues. Here, we will discuss how dynamic imaging techniques have provided unexpected new insight into (i) how immune responses are dynamically regulated by cells and structures in the local tissue environment, (ii) how protective responses to T. gondii are generated and (iii) how the parasite exploits the immune system for its own benefit. [ABSTRACT FROM AUTHOR]

Abstract: There are few studies on human ocular leishmaniasis found in the literature. The purpose of this study was to describe experimental ocular leishmaniasis, caused by Leishmania amazonensis evaluating two different infection routes: intravitreal and instillation in C57BL/10 and BALB/c mice. In this work all animals presented low anti-Leishmania IgM and IgG titers regardless of the infection route or mouse strain. The histopathological eye analysis showed that the mice inoculated by the intravitreal route developed more severe lesions, presenting parasites in the anterior region of the eye 60days after infection. The C57BL/10 mice presented cells containing parasitophorous vacuoles associated with pigmented cells and inflammatory infiltrate, which included mast cells. Ninety days after infection no parasites could be found in either mouse strain, which led us to hypothesize that parasites had been eliminated. In this context, we show that both intravitreal and instillation routes were effective in promoting ocular leishmaniasis infections in C57BL/10 and BALB/c mice. There were no differences in the parasite infection between the two mouse models and it mimicked the ocular lesions described in symptomatic dogs in endemic areas of visceral leishmaniasis. [Copyright &y& Elsevier]

Abstract: ES-62 is an immunomodulatory phosphorylcholine (PC)-containing glycoprotein secreted by the rodent filarial nematode Acanthocheilonema viteae. Previously, the use of knockout mice has revealed the effects of ES-62 on macrophages and dendritic cells to be dependent on TLR4. However, it is possible that ES-62 may interact with additional proteins on the surfaces of target cells and hence that cells may vary with respect to receptor usage. In this study, we identified by molecular weight, proteins that interact with ES-62 and found differences amongst the immune system cells studied. Thus, whereas lymphocytes appear to have two major interacting proteins of ∼135 and ∼82kDa, U937 monocytes only contain an ES-62-binding protein of the latter molecular weight. Binding to the proteins on B cells and U937 cells was blocked by PC, suggesting a critical role for this ES-62 moiety in facilitating interaction. Finally, ES-62 binding is followed by internalization in both macrophages and B cells but only in the former was absence of TLR4 found to block internalization. These findings are consistent with differences in receptor usage by ES-62 amongst different cell-types. [Copyright &y& Elsevier]

Abstract: The intestinal nematode parasite Heligmosomoides polygyrus bakeri exerts widespread immunomodulatory effects on both the innate and adaptive immune system of the host. Infected mice adopt an immunoregulated phenotype, with abated allergic and autoimmune reactions. At the cellular level, infection is accompanied by expanded regulatory T cell populations, skewed dendritic cell and macrophage phenotypes, B cell hyperstimulation and multiple localised changes within the intestinal environment. In most mouse strains, these act to block protective Th2 immunity. The molecular basis of parasite interactions with the host immune system centres upon secreted products termed HES (H. polygyrus excretory–secretory antigen), which include a TGF-β-like ligand that induces de novo regulatory T cells, factors that modify innate inflammatory responses, and molecules that block allergy in vivo. Proteomic and transcriptomic definition of parasite proteins, combined with biochemical identification of immunogenic molecules in resistant mice, will provide new candidate immunomodulators and vaccine antigens for future research. [Copyright &y& Elsevier]

There is no licensed vaccine against any human parasitic disease and apicomplexan parasites cause enormous human suffering; the malaria parasite alone kills approximately one million people annually and is the cause of the majority of infection-related deaths in the young. A malaria vaccine is essential if the goal of malaria eradication is to be achieved. Decades ago it was shown that attenuated malaria parasites could induce sterile immunity to infection but progress towards efficacious vaccines for malaria has been slow. However, recent studies have begun to tease out the immune correlates of vaccine-induced sterile protection and essential research on animal models of disease continues to guide vaccine design. Whole parasite approaches to vaccine design through attenuation as well as subunit vaccine development continue to move forward to clinical trials and are showing promising results. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics related to immunology and cell biology research of parasitic diseases including "The Role of Lipopeptidophosphoglycan in the Immune Response to Entamoeba histolytica," by I. Wong-Baeza et al., "Detection of the Endosomal Sorting Complex Required for Transport in Entamoeba histolytica and Characterization of the EhVps4 Protein," by I. López-Reyes et al., and "Toll-Like Receptor Initiated Host Defense Against Toxoplasma gondii,” by E. Y. Denkers.

The article presents a study regarding the effect of virulent Entamoeba histolytica on respiratory burst potential of macrophages. The author explains that the priming effect of lipopolysaccharide and interferon gamma was inhibited by both crude and purified amoebic proteins. The results indicate that amoebic proteins are capable of modulating macrophage respiratory burst response.

The article focuses on research completed on helminth worms and their ability to infect humans with bacteria and disease. Topics include the helminth's ability to reactivate latent murine herpesvirus in microphages, the susceptibility of humans to viral infection from helminths, and the adaptation of the helminth in response to the immunological status of hosts.

Background: The immune mechanism for subverting the parasitic disease depends on both the innate and cell-mediated immune responses. The role of B-cells in the protection towards the disease could be attributed due to its antibody production, antigen presentation and cytokine production events; they may play a protective or pathological role. This study aims to look for the role of B-cells in induction of immune activation, disease associated anemia and ultimately in parasitemia control. Methods & Materials: The study was performed on whole blood/PBMC and splenic aspirates from VL cases and endemic control group whole blood/PBMC. The aspirates from spleen of patients were obtained for diagnosis and scored upon microscopic examination. Blood from cases and subjected to flow cytometry for assessment of the frequency of B-cell and the costimulatory molecules (CD80 and CD86) along with the activation status (CD25). The measure of humoral responses were assessed through the positive antibody titres by DAT and haemoglobin levels were obtained from the plasma samples of cases. Results: There was significant difference in the frequency of B cells in cases pre- and post-treatment (p=0.0007) however no significant differences were found between the pre-treatment group and the healthy controls. The activation of B-cell was significantly decreased (p=0.009) in VL cases as compared to the healthy controls. The frequency of CD19+ cells with CD80 expression differed between the heathy controls and the post-treated individuals with p-value=0.0013. CD86 expression was significantly higher (p=0.0001) in B-cell population from post-treated as compared to pre-treatment. The splenic score was in accordance with the antibody titres and the haemoglobin levels in the VL cases. Conclusion: We found that the B-cells have important role in driving immune responses demonstrated by the increased frequency as the treatment progresses and gradually resumes the normal level upon cure while the activation upon treatment and persists even after cure. The understanding of the role of B-cells in the infection could be a major breakthrough for designing a therapeutic option which could be of help in the clearance of the infection. [ABSTRACT FROM AUTHOR]

Trypanosoma evansi ( T. evansi) causes a wasting disease in almost all mammals. Trypanosoma evansi infection gives rise to the inflammatory responses that contribute to the development of inflammation-associated tissue injury. To determine what kinds of inflammatory molecules play roles in the pathogenicity of T. evansi infection, polymerase chain reaction array analysis was performed on samples from the infected and uninfected mice. The inflammatory cytokine and chemokine storm, caused mainly by macrophages, was observed. On the other hand, the expression levels of Ccl8 and Il10 in splenocytes were also markedly increased. These results suggested an augmentation in the number and activity of regulatory dendritic cells (DCs). Therefore, the kinetics of regulatory DCs in T. evansi-infected mice were investigated. During T. evansi infection, the regulatory DCs became prevalent, with reducing the amount of inflammatory DCs. Interestingly, when the regulatory DCs were implanted into T. evansi-infected mice, the survival was prolonged, and the expression levels of inflammatory molecules were suppressed. Taken together, these results showed that a subset of regulatory DCs acted as a potential regulator of the inflammatory responses. [ABSTRACT FROM AUTHOR]