Secreted virulence factors and immune evasion in visceral leishmaniasis

Lambertz, Ulrike; Silverman, Judith M.; Nandan, Devki; McMaster, W. Robert; Clos, Joachim; Foster, Leonard J.; Reiner, Neil E.

doi:10.1189/jlb.0611326

Cited by 78 publications

(90 citation statements)

References 121 publications

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“…Epistaxis was the sole exception, possibly a result of the symptom's lack of specificity; in addition to edema and jaundice, it has been identified to be a strong risk factor for death in patients with visceral leishmaniasis. 3,39 Altogether, these observations suggest that disease-induced malnutrition is the main factor contributing to parasite replication, which secondarily may lead to systemic inflammation, depending upon virulence factors and genetically driven host response [40][41][42][43] Therefore, the present data suggest that the association of higher parasitemia with malnutrition and with death may be caused by a nutrition-dependent immunosuppression, leading both to higher parasite burden and to disease severity. However, in opposition to our findings, a previous study 21 found higher bone marrow parasite burden in patients with better prognosis and higher mortality in those with a low parasite load observed by microscopy.…”

Section: Discussionmentioning

confidence: 57%

Bone Marrow Parasite Burden among Patients with New World Kala-Azar is Associated with Disease Severity

Silva¹,

Zacarias

Figueirêdo

et al. 2014

The American Journal of Tropical Medicine and Hygiene

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Abstract. Kala-azar or visceral leishmaniasis, found mostly throughout the Indian Subcontinent, East Africa, and Brazil, kills 20,000-40,000 persons annually. The agents, Leishmania donovani and Leishmania infantum, are obligatory intracellular protozoa of mononuclear phagocytes found principally in the spleen and bone marrow. Protracted fever, anemia, wasting, hepatosplenomegaly, hemorrhages, and bacterial co-infections are typical features. One hundred and twenty-two (122) in-hospital patients were studied to verify if higher bone marrow parasite load estimated by quantitative polymerase chain reaction is associated with severe disease. The estimated median parasite load was 5.0 parasites/ 10 6 human nucleated cells. It is much higher in deceased than among survivors (median 75.0 versus 4.2). Patients who lost more weight had a higher parasite burden, as well as patients with epistaxis, abdominal pain, edema, and jaundice. This study suggests that higher parasite load is influenced by wasting, which may lead to more severe disease.

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Section: Discussionmentioning

confidence: 57%

Bone Marrow Parasite Burden among Patients with New World Kala-Azar is Associated with Disease Severity

Silva¹,

Zacarias

Figueirêdo

et al. 2014

The American Journal of Tropical Medicine and Hygiene

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“…The clearance of Leishmania infection by the innate immune system is dependent primarily upon intracellular killing via superoxide and nitric oxide within phagolysosomes of infected macrophages, which is enhanced by IFN-␥ stimulation from NK cells early in infection and T cells at later stages. The mechanisms of immunity to various species of Leishmania, and the specific evasion mechanisms utilized by Leishmania species, are beyond the scope of this review and have been thoroughly discussed elsewhere (306,307).…”

Section: Leishmaniasis Life Cycle and Mechanisms Of Virulencementioning

confidence: 99%

Transmission and Epidemiology of Zoonotic Protozoal Diseases of Companion Animals

2013

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SUMMARYOver 77 million dogs and 93 million cats share our households in the United States. Multiple studies have demonstrated the importance of pets in their owners' physical and mental health. Given the large number of companion animals in the United States and the proximity and bond of these animals with their owners, understanding and preventing the diseases that these companions bring with them are of paramount importance. Zoonotic protozoal parasites, including toxoplasmosis, Chagas' disease, babesiosis, giardiasis, and leishmaniasis, can cause insidious infections, with asymptomatic animals being capable of transmitting disease.GiardiaandToxoplasma gondii, endemic to the United States, have high prevalences in companion animals.LeishmaniaandTrypanosoma cruziare found regionally within the United States. These diseases have lower prevalences but are significant sources of human disease globally and are expanding their companion animal distribution. Thankfully, healthy individuals in the United States are protected by intact immune systems and bolstered by good nutrition, sanitation, and hygiene. Immunocompromised individuals, including the growing number of obese and/or diabetic people, are at a much higher risk of developing zoonoses. Awareness of these often neglected diseases in all health communities is important for protecting pets and owners. To provide this awareness, this review is focused on zoonotic protozoal mechanisms of virulence, epidemiology, and the transmission of pathogens of consequence to pet owners in the United States.

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“…The T. cruzi small membrane proteins (TcSMP) family of proteins or phosphatases detected on T. cruzi EVs has been shown to trigger Ca 2ϩ signaling and lysosome mobilization/exocytosis, events that promote formation of parasitophorous vacuoles and parasite invasion (36,37). A similar modulation of macrophage responses was observed following exposure to purified Leishmania exosomes, a strategy that enhances intracellular parasite survival (38,39). Mechanistic studies suggest that in the early stages of infection by T. cruzi, parasites promote the release of plasma membrane vesicles from the host cell, which may contribute to parasite survival in the circulatory system, an event thought to help mediate host cell invasion (40).…”

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confidence: 92%

Characterization and Diagnostic Application of Trypanosoma cruzi Trypomastigote Excreted-Secreted Antigens Shed in Extracellular Vesicles Released from Infected Mammalian Cells

et al. 2017

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Chagas disease, caused by Trypanosoma cruzi, although endemic in many parts of Central and South America, is emerging as a global health threat through the potential contamination of blood supplies. Consequently, in the absence of a gold standard assay for the diagnosis of Chagas disease, additional antigens or strategies are needed. A proteomic analysis of the trypomastigote excreted-secreted antigens (TESA) associated with exosomal vesicles shed by T. cruzi identified ϳ80 parasite proteins, with the majority being trans-sialidases. Mass spectrometry analysis of immunoprecipitation products performed using Chagas immune sera showed a marked enrichment in a subset of TESA proteins. Of particular relevance for diagnostic applications were the retrotransposon hot spot (RHS) proteins, which are absent in Leishmania spp., parasites that often confound diagnosis of Chagas disease. Interestingly, serological screens using recombinant RHS showed a robust immunoreactivity with sera from patients with clinical stages of Chagas ranging from asymptomatic to advance cardiomyopathy and this immunoreactivity was comparable to that of crude TESA. More importantly, no cross-reactivity with RHS was detected with sera from patients with malaria, leishmaniasis, toxoplasmosis, or African sleeping sickness, making this protein an attractive reagent for diagnosis of Chagas disease.

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Secreted virulence factors and immune evasion in visceral leishmaniasis

Abstract: Review of leishmania secreted virulence factors and their immune‐modulatory functions, as well as exosome release as a major mechanism for effector secretion and delivery.

Cited by 78 publications

References 121 publications

Bone Marrow Parasite Burden among Patients with New World Kala-Azar is Associated with Disease Severity

Bone Marrow Parasite Burden among Patients with New World Kala-Azar is Associated with Disease Severity

Transmission and Epidemiology of Zoonotic Protozoal Diseases of Companion Animals

Characterization and Diagnostic Application of Trypanosoma cruzi Trypomastigote Excreted-Secreted Antigens Shed in Extracellular Vesicles Released from Infected Mammalian Cells

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