Leishmaniasis is a complex of parasitic protozoan diseases caused by more than 20 different species of parasites from Leishmania genus. Conventional treatments are high costly, and promote a sort of side effects. Besides, protozoan resistance to treatments has been reported. Natural products have been investigated as a source of new therapeutic alternatives, not only acting directly against the parasite but also being able to synergistically act on the host immune system in order to control parasitemia. Gallic acid (GA) and ellagic acid (EA) are plant-derived phenolic compounds which are able to induce antiinflammatory, gastroprotective, and anticarcinogenic activities. Therefore, the antileishmania, cytotoxic, and immunomodulatory activities of GA and EA were evaluated in this study. Both GA and EA were able to inhibit the growth of Leishmania major promastigotes (effective concentration (EC) values 16.4 and 9.8 μg/mL, respectively). The cytotoxicity against BALB/c murine macrophages for GA and EA was also assessed (CC values 126.6 and 23.8 μg/mL, respectively). Interestingly, GA and EA also significantly reduced the infection and infectivity of macrophages infected by L. major (EC values 5.0 and 0.9 μg/mL, respectively), with selectivity index higher than 20. Furthermore, both GA and EA induced high immunomodulatory activity evidenced by the increase of phagocytic capability, lysosomal volume, nitrite release, and intracellular calcium [Ca] in macrophages. Further investigations are reinforced in order to evaluate the therapeutic effects of GA and EA in in vivo experimental infection model of leishmaniasis.
Background Toxoplasmosis is a zoonotic disease that affects humans and warm‐blooded animals. This study describes an outbreak of toxoplasmosis in howler monkeys (Alouatta sp.) and survival of capuchins (Sapajus apella), under the same environmental conditions. Methods Howler monkeys were submitted to post‐mortem examination. Tissue samples were processed to histopathology and immunohistochemistry to detect lesions and tachyzoites of Toxoplasma gondii. Tissue samples were also frozen and submitted to PCR and genotyping of T. gondii. Results Typical lesions were observed in several organs including the liver, lymph node, and brain, with intralesional cysts and tachyzoites of T. gondii demonstrated by immunohistochemistry. T. gondii genomic sequences were amplified by PCR, and genotyping characterized the same T. gondii clone in all howler monkeys. Conclusions Our results support the notion that some species of neotropical primates are highly susceptible to toxoplasmosis and the hypothesis that capuchins (S. apella) may be resistant.
Myracrodruon urundeuva (Engl.) Fr. All., commonly known as "aroeira-do-sertão", is a medicinal plant from Anacardiaceae family. In this study, the chemical composition of M. urundeuva essential oil (MuEO) was evaluated by gas chromatography-mass spectrometry (GC-MS), as well as its anti-Leishmania potential, cytotoxicity, and macrophage activation capability as possible antiprotozoal mechanism of action were assessed. Fourteen compounds were identified, which constituted 94.87% of total oil composition. The most abundant components were monoterpenes (80.35%), with β-myrcene (42.46%), α-myrcene (37.23%), and caryophyllene (4.28%) as the major constituents. The MuEO inhibited the growth of promastigotes (IC 205 ± 13.4 μg mL), axenic amastigotes (IC 104.5 ± 11.82 μg mL) and decreased percentage of macrophage infection and number of amastigotes per macrophage (IC of 44.5 ± 4.37 μg⋅mL), suggesting significant anti-Leishmania activity. The cytotoxicity of MuEO was assessed by MTT test in Balb/c murine macrophages and by human erythrocytes lysis assay and low cytotoxicity for these cells was observed. The CC value against macrophages were 550 ± 29.21 μg mL, while cytotoxicity for erythrocytes was around 20% at the highest concentration assessed, with HC > 800 μg mL. While MuEO-induced anti-Leishmania activity is not mediated by increases in both lysosomal activity and nitric oxide production in macrophages, the results suggest the antiamastigote activity is associated with an immunomodulatory activity of macrophages due to an increase of phagocytic capability induced by MuEO. Thus, MuEO presented significant activity against Leishmania amazonensis, probably modulating the activation of macrophages, with low cytotoxicity to murine macrophages and human erythrocytes.
Background/Objectives Vaccination is the most important tool for controlling brucellosis, but currently there is no vaccine available for canine brucellosis, which is a zoonotic disease of worldwide distribution caused by Brucella canis. This study aimed to evaluate protection and immune response induced by Brucella ovis ΔabcBA (BoΔabcBA) encapsulated with alginate against the challenge with Brucella canis in mice and to assess the safety of this strain for dogs. Methods Intracellular growth of the vaccine strain BoΔabcBA was assessed in canine and ovine macrophages. Protection induced by BoΔabcBA against virulent Brucella canis was evaluated in the mouse model. Safety of the vaccine strain BoΔabcBA was assessed in experimentally inoculated dogs. Results Wild type B. ovis and B. canis had similar internalization and intracellular multiplication profiles in both canine and ovine macrophages. The BoΔabcBA strain had an attenuated phenotype in both canine and ovine macrophages. Immunization of BALB/c mice with alginateencapsulated BoΔabcBA (10 8 CFU) induced lymphocyte proliferation, production of IL-10 and IFN-γ, and protected against experimental challenge with B. canis. Dogs immunized with alginate-encapsulated BoΔabcBA (10 9 CFU) seroconverted, and had no hematologic, biochemical or clinical changes. Furthermore, BoΔabcBA was not detected by isolation or PCR performed using blood, semen, urine samples or vaginal swabs at any time point over the course of this study. BoΔabcBA was isolated from lymph nodes near to the site of inoculation in two dogs at 22 weeks post immunization.
Yellow fever is an important zoonotic viral disease that can be fatal for both human and nonhuman primates. We evaluated histopathologic changes in free-ranging neotropical primates naturally infected with yellow fever virus (YFV) compared with uninfected cohorts. The most frequent lesions in primates infected with YFV were hepatic changes characterized by midzonal necrosis with lipidosis and mild inflammation including lymphocytes, macrophages, plasma cells, and infrequently neutrophils. Importantly, severe necrotizing hepatic lesions were often observed in Alouatta sp. (howler monkeys), whereas Callithrix sp. (common marmosets) had nearly no hepatic changes. Moderate to severe hepatic necrosis was present in 21/23 (91%) of the YFV-positive Alouatta sp. compared with 10/29 (34%) of the YFV-positive Callithrix sp. ( P < .0001; odds ratio = 20). Similarly, hepatitis was more intense in Alouatta sp. compared with Callithrix sp. Furthermore, the frequency of YFV infection was significantly higher in Alouatta sp. compared with Callithrix sp. or Sapajus sp. (capuchin monkeys). Therefore, these data support the notion that Alouatta sp. is highly susceptible to infection and YFV-induced lesions, whereas Callithrix sp. is susceptible to infection but has a lower frequency of YFV-induced lesions.
The diseases caused by Salmonella Gallinarum and S. Pullorum in chickens known as fowl typhoid and pullorum disease, respectively, pose a great threat to the poultry industry mainly in developing countries, since they have already been controlled in the developed ones. These bacteria are very similar at the genomic level but develop distinct host-pathogen relationships with chickens. Therefore, a deep understanding of the molecular mechanisms whereby S. Gallinarum and S. Pullorum interact with the host could lead to the development of new approaches to control and, perhaps, eradicate both diseases from the chicken flocks worldwide. Based on our previous study, it was hypothesised that metabolism-related pseudogenes, fixed in S. Pullorum genomes, could play a role in the distinct host-pathogen interaction with susceptible chickens. To test this idea, three genes (idnT, idnO and ccmH) of S. Gallinarum str. 287/91, which are pseudogenes on the S. Pullorum chromosomes, were inactivated by mutations. These genetically engineered strains grew well on the solid media without any colony morphology difference. In addition, similar growth curves were obtained by cultivation in M9 minimal medium containing D-gluconate as the sole carbon source. Infection of chickens with idnTO mutants led to increased numbers of bacteria in the livers and spleens at 5 days post-infection, but with slightly decreased heterophil infiltration in the spleens when compared to the wild-type strain. On the other hand, no significant phenotypic change was caused by mutation to ccmH genes. Apart from the above-mentioned alterations, all S. Gallinarum strains provoked similar infections, since mortality, clinical signs, macroscopic alterations and immune response were similar to the infected chickens. Therefore, according to the model applied to this study, mutation to the idnTO and ccmH genes showed minor impact on the fowl typhoid pathogenesis and so they may be relics from the ancestor genome. Our data hints at a more complex mechanism driving the distinct host-pathogen interaction of S. Gallinarum/Pullorum with chickens than differential inactivation of a few genes.
Mammaliicoccus (Staphylococcus) sciuri has been rarely associated with infections and sepsis in humans. A 3‐month‐old male western lowland gorilla (Gorilla gorilla gorilla), born under human care, died after a traumatic event. Histologic, microbiologic, and molecular findings in postmortem demonstrated a suppurative meningoencephalitis and bacteremia associated with M. sciuri infection.
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