Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensis
Cysteinyl leukotrienes (CysLTs) and lipoxins (LXs) are lipid mediators that control inflammation, with the former inducing and the latter inhibiting this process. Because the role played by these mediators in paracoccidioidomycosis was not investigated, we aimed to characterize the role of CysLT in...
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| Format: | Article |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/852574 |
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| author | Laura R. R. Ribeiro Flávio V. Loures Eliseu F. de Araújo Cláudia Feriotti Tânia A. Costa Carlos Henrique Serezani Sonia Jancar Vera L. G. Calich |
| author_facet | Laura R. R. Ribeiro Flávio V. Loures Eliseu F. de Araújo Cláudia Feriotti Tânia A. Costa Carlos Henrique Serezani Sonia Jancar Vera L. G. Calich |
| author_sort | Laura R. R. Ribeiro |
| collection | DOAJ |
| description | Cysteinyl leukotrienes (CysLTs) and lipoxins (LXs) are lipid mediators that control inflammation, with the former inducing and the latter inhibiting this process. Because the role played by these mediators in paracoccidioidomycosis was not investigated, we aimed to characterize the role of CysLT in the pulmonary infection developed by resistant (A/J) and susceptible (B10.A) mice. 48 h after infection, elevated levels of pulmonary LTC4 and LXA4 were produced by both mouse strains, but higher levels were found in the lungs of susceptible mice. Blocking the CysLTs receptor by MTL reduced fungal loads in B10.A, but not in A/J mice. In susceptible mice, MLT treatment led to reduced influx of PMN leukocytes, increased recruitment of monocytes, predominant synthesis of anti-inflammatory cytokines, and augmented expression of 5- and 15-lipoxygenase mRNA, suggesting a prevalent LXA4 activity. In agreement, MTL-treated macrophages showed reduced fungal burdens associated with decreased ingestion of fungal cells. Furthermore, the addition of exogenous LX reduced, and the specific blockade of the LX receptor increased the fungal loads of B10.A macrophages. This study showed for the first time that inhibition of CysLTs signaling results in less severe pulmonary paracoccidioidomycosis that occurs in parallel with elevated LX activity and reduced infection of macrophages. |
| format | Article |
| id | doaj-art-0ec92d7dad894726ae3c2f499c332986 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-0ec92d7dad894726ae3c2f499c3329862025-02-03T01:21:29ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/852574852574Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensisLaura R. R. Ribeiro0Flávio V. Loures1Eliseu F. de Araújo2Cláudia Feriotti3Tânia A. Costa4Carlos Henrique Serezani5Sonia Jancar6Vera L. G. Calich7Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Avenida Professor Lineu Prestes 1730, 05508-900 São Paulo, SP, BrazilDepartamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Avenida Professor Lineu Prestes 1730, 05508-900 São Paulo, SP, BrazilDepartamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Avenida Professor Lineu Prestes 1730, 05508-900 São Paulo, SP, BrazilDepartamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Avenida Professor Lineu Prestes 1730, 05508-900 São Paulo, SP, BrazilDepartamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Avenida Professor Lineu Prestes 1730, 05508-900 São Paulo, SP, BrazilDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Avenida Professor Lineu Prestes 1730, 05508-900 São Paulo, SP, BrazilDepartamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Avenida Professor Lineu Prestes 1730, 05508-900 São Paulo, SP, BrazilCysteinyl leukotrienes (CysLTs) and lipoxins (LXs) are lipid mediators that control inflammation, with the former inducing and the latter inhibiting this process. Because the role played by these mediators in paracoccidioidomycosis was not investigated, we aimed to characterize the role of CysLT in the pulmonary infection developed by resistant (A/J) and susceptible (B10.A) mice. 48 h after infection, elevated levels of pulmonary LTC4 and LXA4 were produced by both mouse strains, but higher levels were found in the lungs of susceptible mice. Blocking the CysLTs receptor by MTL reduced fungal loads in B10.A, but not in A/J mice. In susceptible mice, MLT treatment led to reduced influx of PMN leukocytes, increased recruitment of monocytes, predominant synthesis of anti-inflammatory cytokines, and augmented expression of 5- and 15-lipoxygenase mRNA, suggesting a prevalent LXA4 activity. In agreement, MTL-treated macrophages showed reduced fungal burdens associated with decreased ingestion of fungal cells. Furthermore, the addition of exogenous LX reduced, and the specific blockade of the LX receptor increased the fungal loads of B10.A macrophages. This study showed for the first time that inhibition of CysLTs signaling results in less severe pulmonary paracoccidioidomycosis that occurs in parallel with elevated LX activity and reduced infection of macrophages.http://dx.doi.org/10.1155/2015/852574 |
| spellingShingle | Laura R. R. Ribeiro Flávio V. Loures Eliseu F. de Araújo Cláudia Feriotti Tânia A. Costa Carlos Henrique Serezani Sonia Jancar Vera L. G. Calich Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensis Mediators of Inflammation |
| title | Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensis |
| title_full | Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensis |
| title_fullStr | Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensis |
| title_full_unstemmed | Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensis |
| title_short | Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensis |
| title_sort | lipoxin inhibits fungal uptake by macrophages and reduces the severity of acute pulmonary infection caused by paracoccidioides brasiliensis |
| url | http://dx.doi.org/10.1155/2015/852574 |
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