ArticlePLoS neglected tropical diseases2013
The pivotal role of 5-lipoxygenase-derived LTB4 in controlling pulmonary paracoccidioidomycosis.
Article in PLoS neglected tropical diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- Activation of leukotriene BCellular & molecular immunology · 2024Article
- Toxoplasma gondii Infection Decreases Intestinal 5-Lipoxygenase Expression, while Exogenous LTBInfection and immunity · 2022Article
- Circulating Nestin-GFPStem cell reviews and reports · 2021Article
- Article
- Article
- Excessive localized leukotriene B4 levels dictate poor skin host defense in diabetic mice.JCI insight · 2018Article
- Neutrophils: Beneficial and Harmful Cells in Septic Arthritis.International journal of molecular sciences · 2018Review
- Leukotriene BScientific reports · 2017Article
- Too much of a good thing: How modulating LTBSeminars in immunology · 2017Review
- Influenza A Virus as a Predisposing Factor for Cryptococcosis.Frontiers in cellular and infection microbiology · 2017Article
- Host-Derived Leukotriene BFrontiers in immunology · 2017Article
- 5-Lipoxygenase negatively regulates Th1 response during Brucella abortus infection in mice.Infection and immunity · 2015Article
- Resistance to P. brasiliensis Experimental Infection of Inbred Mice Is Associated with an Efficient Neutrophil Mobilization and Activation by Mediators of Inflammation.Mediators of inflammation · 2015Article
- Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensis.Mediators of inflammation · 2015Article
- Protective role of 5-lipoxigenase during Leishmania infantum infection is associated with Th17 subset.BioMed research international · 2014Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leukotrienes (LTs) produced from arachidonic acid by the action of 5-lipoxygenase (5-LO) are classical mediators of inflammatory responses. However, studies published in the literature regarding these mediators are contradictory and it remains uncertain whether these lipid mediators play a role in host defense against the fungal pathogen Paracoccidioides brasiliensis. To determine the involvement of LTs in the host response to pulmonary infection, wild-type and LT-deficient mice by targeted disruption of the 5-lipoxygenase gene (knockout mice) were studied following intratracheal challenge with P. brasiliensis yeasts. The results showed that infection is uniformly fatal in 5-LO-deficient mice and the mechanisms that account for this phenotype are an exacerbated lung injury and higher fungal pulmonary burden. Genetic ablation or pharmacological inhibition of LTs resulted in lower phagocytosis and fungicidal activity of macrophages in vitro, suggesting that deficiency in fungal clearance seems to be secondary to the absence of activation in 5-LO(-/-) macrophages. Exogenous LTB4 restored phagocytosis and fungicidal activity of 5-LO(-/-) macrophages. Moreover, P. brasiliensis killing promoted by LTB4 was dependent on nitric oxide (NO) production by macrophages. Taken together, these results reveal a fundamental role for 5-LO-derived LTB4 in the protective response to P. brasiliensis infection and identify relevant mechanisms for the control of fungal infection during the early stages of the host immune response.
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