Evidence That Lipopolisaccharide May Contribute to the Cytokine Storm and Cellular Activation in Patients with Visceral Leishmaniasis
| العنوان: | Evidence That Lipopolisaccharide May Contribute to the Cytokine Storm and Cellular Activation in Patients with Visceral Leishmaniasis |
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| المؤلفون: | Rivaldo Venâncio da Cunha, Alda Maria Da-Cruz, C. R. B. Leal, Patrícia T. Bozza, Eduardo G. Regis, Joanna Reis Santos-Oliveira |
| المصدر: | PLoS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, Vol 5, Iss 7, p e1198 (2011) |
| بيانات النشر: | Public Library of Science (PLoS), 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Adult, Lipopolysaccharides, Male, lcsh:Arctic medicine. Tropical medicine, Adolescent, lcsh:RC955-962, medicine.medical_treatment, Immunology, Lymphocyte Activation, Young Adult, medicine, Humans, Lymphocyte Count, Macrophage Migration-Inhibitory Factors, Biology, Immunoassay, Leishmania, Bacteria, biology, lcsh:Public aspects of medicine, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Leishmaniasis, Immunosuppression, Middle Aged, Flow Cytometry, medicine.disease, biology.organism_classification, Intramolecular Oxidoreductases, Infectious Diseases, Visceral leishmaniasis, Bacterial Translocation, Cytokines, Leishmaniasis, Visceral, Medicine, Female, Clinical Immunology, Macrophage migration inhibitory factor, Lymphocytopenia, Cytokine storm, Cell activation, Research Article |
| الوصف: | Background Visceral leishmaniasis (VL) is characterized by parasite-specific immunosuppression besides an intense pro-inflammatory response. Lipopolisaccharide (LPS) has been implicated in the immune activation of T-cell deficient diseases such as HIV/AIDS and idiopathic lymphocytopenia. The source of LPS is gram-negative bacteria that enter the circulation because of immunological mucosal barrier breakdown. As gut parasitization also occurs in VL, it was hypothesized that LPS may be elevated in leishmaniasis, contributing to cell activation. Methodology/Principal Findings Flow cytometry analysis and immunoassays (ELISA and luminex micro-beads system) were used to quantify T-cells and soluble factors. Higher LPS and soluble CD14 levels were observed in active VL in comparison to healthy subjects, indicating that LPS was bioactive; there was a positive correlation between these molecules (r = 0.61;p Author Summary Visceral leishmaniasis (VL) affects organs rich in lymphocytes, being characterized by intense Leishmania-induced T-cell depletion and reduction in other hematopoietic cells. In other infectious and non-infectious diseases in which the immune system is affected, such as HIV-AIDS and inflammatory bowel disease, damage to gut-associated lymphocyte tissues occurs, enabling luminal bacteria to enter into the circulation. Lipopolisaccharide (LPS) is a bacterial product that stimulates macrophages, leading to the production of pro-inflammatory cytokines and other soluble factors such as MIF, which in turn activate lymphocytes. Continuous and exaggerated stimulation causes exhaustion of the T-cell compartment, contributing to immunosuppression. Herein, we show that an increment in LPS plasma levels also occurs in VL; the higher the LPS levels, the lower the TCD4+ and TCD8+ cell count in the blood. This T-cell depletion may affect the mucosal immune system, which, along with intestinal parasitization by amastigotes, may contribute to gut barrier damage and consequent microbial translocation. LPS levels were correlated with T-cell activation, pro-inflammatory cytokine plasma levels, MIF, and IFABP, showing that a bacterial molecule, probably from luminal origin, not associated with Leishmania infection can negatively affect the immune system. These findings points to possible benefits of antimicrobial prophylaxis in conjunction with anti-Leishmania therapy. |
| تدمد: | 1935-2735 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::371ef13fad8b63fd506a0cf403c12381Test https://doi.org/10.1371/journal.pntd.0001198Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....371ef13fad8b63fd506a0cf403c12381 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19352735 |
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