Leishmania infantum infection reduces the amyloid β42-stimulated NLRP3 inflammasome activation

Activation of the NLRP3 inflammasome has been shown to play a major role in the neuroinflammation that accompanies Alzheimer’s disease (AD); interventions that down regulate the NLRP3 inflammasome could thus be beneficial in AD. Parasite infections were recently shown to be associated with improved cognitive functions in Apolipoprotein E4 (ApoE4)-expressing members of an Amazonian tribe. We verified in an in vitro model whether Leishmania infantum infection could reduce NLRP3. Results obtained in an initial experimental model in which PBMC were LPS primed and nigericin-stimulated showed that L. infantum infection significantly reduced ASC-speck formation (i.e. intracellular inflammasome proteins assembly), as well as the production of activated caspase 5 and IL-1β, but increased that of activated caspase 1 and IL-18. Moreover, L. infantum infection induced the generation of an anti-inflammatory milieu by suppressing the production of TNFα and increasing that of IL-10. These results were replicated when cells that had been LPS-primed were stimulated with Aβ₄₂ and infected with L. infantum. Results herein indicate that Leishmania infection favors an anti-inflammatory milieu, which includes the down-regulation of NLRP3 inflammasome activation, possibly to facilitate its survival inside host cells. A side effect of Leishmaniasis would be the hampering of neuroinflammation; this could play a protective role against AD development.     

Serum proteome of dogs at subclinical and clinical onset of canine leishmaniosis

The objective of this study was to identify changes in serum proteome in dogs that may occur after an experimental infection at subclinical and clinical stages of canine leishmaniosis (CanL). For this purpose, canine pre‐ and post‐infection with Leishmania infantum serum proteomes in the same dogs were analysed by a high‐throughput label‐based quantitative LC‐MS/MS proteomic approach. A total of 169 proteins were identified, and 74 of them including complement C8 alpha chain, adiponectin, transferrin, sphingomyelin phosphodiesterase acid‐like 3A and immunoglobulins showed different modulation between the different stages of CanL. These proteins could be considered as potential serum biomarkers of early diagnostic or disease progression in CanL. Additionally, biological pathways modulated during CanL such as blood coagulation or gonadotropin‐releasing hormone receptor were revealed, which could help to understand the pathological mechanisms of the disease.     

Leishmaniasis in cat shelters: A serological,molecular and entomological study

An epidemiological Leishmania spp. and entomological Phlebotomine sandflies survey was performed in cat shelters at leishmaniasis endemic area of Brazil. Blood and conjunctival swab (CS) samples were collected from 94 cats in two animal protection shelters. These samples were subjected to serological tests using the indirect immunofluorescence antibody test (IFAT) and indirect enzyme‐linked immunosorbent assay (ELISA) and to molecular test by polymerase chain reaction (PCR). In addition, a Phlebotomine sandflies survey was performed in the same shelters. The analyses revealed a positivity of 31.91% (30/94) through ELISA and 29.79% (28/94) through IFAT. The two serological tests showed a positive association with perfect agreement (k = 0.925). None of the cats were positive by Leishmania spp. DNA. One Lutzomyia (Lutzomyia) longipalpis male was found in one of the cat shelters. The results and the implications of our findings are discussed below.     

Evaluation of Apoptotic and Antileishmanial Activities of Artemisinin on Promastigotes and BALB/C Mice Infected with Leishmania major

Background:

In leishmaniasis, some drugs prescribed for treatment have toxic effects and there are reports about drug resistance in some countries. Due to this fact, using herbal drugs such as artemisinin with good efficacy and low toxic effect might be suitable.

Methods:

We evaluated the apoptotic effect of artemisinin on Leishmania major in vitro and the antileishmanial activities of artemisinin on leishmaniasis in BALB/c mice and at the end INF-γ and IL-4 cytokines levels were detected by ELISA in spleen cell culture supernatants. During treatment the lesion size and survival rate were measured each four and ten days, respectively.

Results:

Percentage of early and late apoptosis in promastigotes of control group and promastigotes treated with 10, 25, 50 and 100 μg/ml of artemisinin after 48 h were 0.13, 16.04, 41.23, 49.03 and 81.83, respectively. The IFN-γ in ointment treated group were higher than those of other groups (P<0.05). The in vivo results showed that ointment compounds healed the lesions more effectively rather than intraperitoneal injection method (P<0.05). The survival rate of mice 150 days after challenge in treated group with ointment of artemisinin was 66% while all mice in control groups were died.

Conclusion:

All of in vitro results represented that this drug had antileishmanial effects and these results were confirmed by evaluation effects in vivo condition of leishmaniasis. Interestingly, according to these results it can be concluded that this drug has antileishmanial effects in vitro and in vivo conditions. Artemisinin induces cytotoxic effect on L. major via apoptosis-related mechanism.     

Permissive and protective roles for neutrophils in leishmaniasis

Leishmania parasites are the causative agents of leishmaniasis, a neglected tropical disease that causes substantial morbidity and considerable mortality in many developing areas of the world. Recent estimates suggest that roughly 10 million people suffer from cutaneous leishmaniasis (CL), and approximately 76 000 are afflicted with visceral leishmaniasis (VL), which is universally fatal without treatment. Efforts to develop therapeutics and vaccines have been greatly hampered by an incomplete understanding of the parasite's biology and a lack of clear protective correlates that must be met in order to achieve immunity. Although parasites grow and divide preferentially in macrophages, a number of other cell types interact with and internalize Leishmania parasites, including monocytes, dendritic cells and neutrophils. Neutrophils appear to be especially important shortly after parasites are introduced into the skin, and may serve a dual protective and permissive role during the establishment of infection. Curiously, neutrophil recruitment to the site of infection appears to continue into the chronic phase of disease, which may persist for many years. The immunological impact of these cells during chronic leishmaniasis is unclear at this time. In this review we discuss the ways in which neutrophils have been observed to prevent and promote the establishment of infection, examine the role of anti‐neutrophil antibodies in mouse models of leishmaniasis and consider recent findings that neutrophils may play a previously unrecognized role in influencing chronic parasite persistence.     

Acquisition and biosynthesis of saturated and unsaturated fatty acids by trypanosomatids

As components of phospholipids and glycosylphosphatidylinositol anchors, fatty acids are responsible for forming the core of biological membranes and the correct localization of proteins within membranes. They also contribute to anchoring proteins by direct acylation of specific amino acids. Fatty acids can be used as energy sources and serve as signaling molecules or precursors for their synthesis. All these processes highlight the important role of fatty acids in cell physiology, justifying the diverse strategies for their acquisition evolved by different organisms. This review describes several recent findings in the salvage and biosynthesis of fatty acids by parasitic protists belonging to the class Kinetoplastea. They include two biosynthetic routes, the mitochondrial one and a peculiar membrane-associated pathway, the synthesis of polyunsaturated fatty acids, and the scavenging of lysophospholipids and lipoproteins from host plasma. These different processes are also explored as putative targets for chemotherapy.     

High infection frequency,low diversity of Leishmania major and first detection of Leishmania turanica in human in northern Iran

Smears of suspected patients infected with zoonotic cutaneous leishmaniasis (ZCL) were stained and examined under a light microscopic observation. DNA of parasites within human ulcers was extracted directly from their smears. Nested PCR was used to amplify a fragment containing the internal transcribed spacers of the ribosomal RNA genes (ITS-rDNA) of Lesihmania parasites in human from Turkemen Sahara located in the northeastern part of Iran. Based on RFLP method by digesting BsuRI restriction enzyme and more precisely sequencing of DNA ITS-rDNA was shown to be species-specific. The infection rates of Leishmania parasites were high with 154 (93.9%) infections out of 164 suspected patients using microscopic observations. Only from 128 suspected patients out of 164, ITS-rDNA fragments were amplified and 125 samples had enough DNA to digest BsuRI restriction enzyme and do DNA sequencing. The Nested PCR assays detected not only Leishmania major but also Leishmania turanica for the first time, another parasite of the great gerbil in human. The density of L. major was high but the diversity was low with only 2 haplotypes. The overall ratio of L. major (123 infections) to L. turanica (2 infections) was significantly higher (Chi-squared test: p < 0.05). Infections of L. turanica are not reported only and/or not known to cause human disease. Our analytical framework conveys a clear understanding of both L. major and L. turanica which can only be approved as causative agents of ZCL by more extensive sampling and followed by standardized molecular diagnosis.     

Apoptosis driven infection

Professional phagocytes like polymorphonuclear neutrophil granulocytes (PMN) and macrophages (MF) kill pathogens as the first line of defense. These cells possess numerous effector mechanisms to eliminate a threat at first contact. However, several microorganisms still manage to evade phagocytic killing, survive and retain infectivity. Some pathogens have developed strategies to silently infect their preferred host phagocytes. The best example of an immune silencing phagocytosis process is the uptake of apoptotic cells. Immune responses are suppressed by the recognition of phosphatidylserine (PS) on the outer leaflet of their plasma membrane. Taking Leishmania major as a prototypic intracellular pathogen, we showed that these organisms can use the apoptotic “eat me” signal PS to silently enter PMN. PS-positive and apoptotic parasites, in an altruistic way, enable the intracellular survival of the viable parasites. Subsequently these pathogens again use PS exposition, now on infected PMN, to silently invade their definitive host cells, the MF. In this review, we will focus on L. major evasion strategies and discuss other pathogens and their use of the apoptotic “eat me” signal PS to establish infection.