Influence of low-density lipoprotein (LDL) receptor on lipid composition, inflammation and parasitism during Toxoplasma gondii infection

Portugal, Luciane R.; Fernandes, Liliam; Pedroso, Vinicius Sousa Pietra; Santiago, Helton da Costa; Gazzinelli, Ricardo T.; Alvarez-Leite, Jacqueline I.

doi:10.1016/j.micinf.2007.12.001

Cited by 60 publications

(44 citation statements)

References 27 publications

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“…As FMs appear among M. tuberculosis/PPD/TDM granuloma, there might be a resemblance in tuberculous granuloma structure arising from these determinants and keto-MA. Pathogen-induced FMs have been reported in cases of Chlamydia (49) and toxoplasma infections (50) and in diseases such as atherosclerosis (51). It is tempting to speculate that the lipid-metabolite-host LSNR cellular deregulation observed in TB and atherosclerosis (28,52) could be generic to other infections and diseases.…”

Section: Discussionmentioning

confidence: 98%

Mycobacterium tuberculosisKeto-Mycolic Acid and Macrophage Nuclear Receptor TR4 Modulate Foamy Biogenesis in Granulomas: A Case of a Heterologous and Noncanonical Ligand-Receptor Pair

Dkhar

Nanduri

Mahajan

et al. 2014

The Journal of Immunology

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The cell wall of Mycobacterium tuberculosis is configured of bioactive lipid classes that are essential for virulence and potentially involved in the formation of foamy macrophages (FMs) and granulomas. Our recent work established crosstalk between M. tuberculosis cell wall lipids and the host lipid-sensing nuclear receptor TR4. In this study, we have characterized, identified, and adopted a heterologous ligand keto-mycolic acid from among M. tuberculosis lipid repertoire for the host orphan NR TR4. Crosstalk between cell wall lipids and TR4 was analyzed by transactivation and promoter reporter assays. Mycolic acid (MA) was found to transactivate TR4 significantly compared with other cell wall lipids. Among the MA, the oxygenated form, keto-MA, was responsible for transactivation, and the identity was validated by TR4 binding assays followed by TLC and nuclear magnetic resonance. Isothermal titration calorimetry revealed that keto-MA binding to TR4 is energetically favorable. This keto-MA–TR4 axis seems to be essential to this oxygenated MA induction of FMs and granuloma formation as evaluated by in vitro and in vivo model of granuloma formation. TR4 binding with keto-MA features a unique association of host nuclear receptor with a bacterial lipid and adds to the presently known ligand repertoire beyond dietary lipids. Pharmacologic modulation of this heterologous axis may hold promise as an adjunct therapy to frontline tuberculosis drugs.

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Section: Discussionmentioning

confidence: 98%

Mycobacterium tuberculosisKeto-Mycolic Acid and Macrophage Nuclear Receptor TR4 Modulate Foamy Biogenesis in Granulomas: A Case of a Heterologous and Noncanonical Ligand-Receptor Pair

Dkhar

Nanduri

Mahajan

et al. 2014

The Journal of Immunology

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“…However toxoplasmosisdecreased serum cholesterol levels in infected does and this finding was in consistence with that of Azhar et al (2012) who indicated that T. gondii decreases serum cholesterol and triglyceride and LDL levels, while increases serum HDL level. T. gondii alters host cell metabolism because it uses host metabolic products for its own metabolic pathways (Al-Kennany et al, 2007) as Toxoplasma cannot synthesize cholesterol and depends upon acquisition of LDL derived from the host cells (Coppens et al, 2000;Portugal et al, 2008). These differences in effect of toxoplasma gondii on the triglycerides and total cholesterol levels in sheep and goats may attributed to the difference in the stage of the disease as acute parasitic infection results in decreased levels of HDL and LDL and moderately increased triglycerides (Nilson et al, 1990;Khovidhunkit et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Seroprevalence of Abortion Causing Agents in Egyptian Sheep and Goat Breeds and Their Effects on the Animal’s Performance

Mahboub¹,

Helal²,

Eldaim

et al. 2013

JAS

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This study was carried out to illustrate seroprevalence of Toxoplasma gondii and Brucella melitensis in local sheep and goat flocks living in Nile Delta regions of Egypt as well as to investigate its effects on animals' health and performance. In trial 1: 492 serum samples were collected from domestic ewes and does flocks suffering from abortion and stillbirths were used in this survey. In trial (2): 100 serum samples collected from toxoplasma or brucella infected or non infected sheep and goats were used to study the effects of toxoplasmosis and brucellosis on animals , health. This study revealed that 142 (28.86%) sera contained antibodies against Toxoplasma gondii and 89 (18.09%) were positive for Brucella melitensis. The incidences of toxoplasmosis and brucellosis were 31.01% and 12.26% in sheep, respectively and 17.11% and 36.84% in goats, respectively. Higher seroprevalence of Toxoplasma gondii was recorded in sheep with high flock size. Farmers using set stocking management had lower seroprevalence toxoplasmosis and brucellosis. Toxoplasmosis and brucellosis lowered serum albumin level and liver enzymes activities while, increased serum levels of globulin, urea, triglyceride and cholesterol in ewes. Serum levels of total protein, albumin and urea and the activity of serum aspartate amino transferase were decreased, however serum level of C reactive protein was increased in infected does. These results indicated that toxoplasmosis is widely spread than brucellosis in small ruminants living in the provinces of Nile Delta. Both toxoplasmosis and brucellosis inversely affected animals' health. Management practices had a role in spread of these agents.

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“…Lipid hydroperoxides (LOOH) are by-products of lipid peroxidation and increased levels of lipid peroxidation products are associated with variety of diseases including parasitic infestations (Kiral et al 2005). Lipid peroxidation can be harmful for skin due to alterations in the structure and permeability (Portugal et al 2008). The elevated levels of MDA in Psoroptes-infested rabbits signify the lipid peroxide-mediated skin lesions.…”

Section: Discussionmentioning

confidence: 99%

Psoroptes cuniculi induced oxidative imbalance in rabbits and its alleviation by using vitamins A, D3, E, and H as adjunctive remedial

Singh

Dimri

Sharma

et al. 2011

Trop Anim Health Prod

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The oxidant/antioxidant balance of rabbits naturally infected with Psoroptes cuniculi and treated with ivermectin +/- vitamins A, D(3), E, and H supplementation was investigated. Two groups of seven mixed ♂ and ♀, 6-to-8 month-old New Zealand White rabbits, diagnosed Psoroptes mites-positive by skin scraping examination and seven clinically healthy control rabbits were examined. Blood samples were obtained on day 0 and at 28 days post-therapy to determine oxidative stress indices. On day 0, the levels of lipid peroxides were significantly higher (P ≤ 0.01) in the Psoroptes-infected rabbits compared with the healthy controls while those of reduced glutathione and the activities of the antioxidant enzymes glutathione peroxidase, glutathione-S-transferase, catalase, and superoxide dismutase were significantly lower (P ≤ 0.01). Vitamin supplementation of the ivermectin-treated rabbits revealed both faster clinical (14 days) and parasitological (10 days) recovery. It was concluded that significant alteration of oxidant/antioxidant balance is a factor in the pathogenesis of P. cuniculi infestation of rabbits, and recovery can be enhanced by combining ivermectin treatment with vitamin A, D(3,) E, and H supplementation.

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Influence of low-density lipoprotein (LDL) receptor on lipid composition, inflammation and parasitism during Toxoplasma gondii infection

Cited by 60 publications

References 27 publications

Mycobacterium tuberculosisKeto-Mycolic Acid and Macrophage Nuclear Receptor TR4 Modulate Foamy Biogenesis in Granulomas: A Case of a Heterologous and Noncanonical Ligand-Receptor Pair

Mycobacterium tuberculosisKeto-Mycolic Acid and Macrophage Nuclear Receptor TR4 Modulate Foamy Biogenesis in Granulomas: A Case of a Heterologous and Noncanonical Ligand-Receptor Pair

Seroprevalence of Abortion Causing Agents in Egyptian Sheep and Goat Breeds and Their Effects on the Animal’s Performance

Psoroptes cuniculi induced oxidative imbalance in rabbits and its alleviation by using vitamins A, D3, E, and H as adjunctive remedial

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