Differential expression of TLRs 2, 4, 9, iNOS and TNF-α and arginase activity in peripheral blood monocytes from glucantime unresponsive and responsive patients with anthroponotic cutaneous leishmaniasis caused by Leishmania tropica

Oliaee, Razieh Tavakoli; Sharifi, Iraj; Afgar, Ali; Jafarzadeh, Abdollah; Kareshk, Amir Tavakoli; Bamorovat, Mehdi; Sharifi, Hamid; Babaei, Zahra; Keyhani, Amir; Keyhani, Alireza; Abedi, Leili; Sharifi, Farshad

doi:10.1016/j.micpath.2018.11.004

Cited by 16 publications

(9 citation statements)

References 53 publications

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“…Host immune response factors -Decreased expression of Th1 (IL-12 P40, IL-1β, TNF, IFN-γ) and increased expression of Th2 (IL-4, IL-10, IL-13, IL-9); other inflammation profiles involved in immune response (Bamorovat et al, 2019a;Oliaee et al, 2019).…”

Section: Demographic Risk Factorsmentioning

confidence: 99%

“…These findings suggest that the TLR2 defect causes disease exacerbation and parasite growth through the enhanced Th2 cell-related responses. However, it has been indicated that the neutrophils of unresponsive CL patients expressed higher levels of TLR2, TLR4, and TLR9 compared to the neutrophils of asymptomatic patients (leishmanin skin-test positive) or healthy individuals (Halliday et al, 2016;Oliaee et al, 2018Oliaee et al, , 2019. However, the TLR2-related impacts can be influenced by parasite species, ligand density, and the signals coming from other PRRs (Jafarzadeh et al, 2019).…”

Section: Host Immune Responsesmentioning

confidence: 99%

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Determinants of Unresponsiveness to Treatment in Cutaneous Leishmaniasis: A Focus on Anthroponotic Form Due to Leishmania tropica

et al. 2021

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Cutaneous leishmaniasis (CL) is a curable disease; however, due to various risk factors, unresponsiveness to CL treatments is inevitable. The treatment of CL has been firmly correlated with multiple determinants, such as demographical, clinical, and environmental factors, the host’s immune response, poor treatment adherence, the parasite’s genetic make-up, and Leishmania RNA virus. This study primarily focuses on the risk factors associated with different therapeutic outcomes following meglumine antimoniate (MA; Glucantime®) treatment and policy approaches to prevent unresponsiveness in CL patients with a focus on anthroponotic form (ACL). Findings suggest that effective preventive and therapeutic measures should be more vigorously implemented, particularly in endemic areas. Accordingly, extensive training is essential to monitor drug unresponsiveness regularly, especially in tropical regions where the disease is prevalent. Since humans are the fundamental reservoir host of ACL due to L. tropica, prompt detection, early diagnosis, and timely and effective treatment could help control this disease. Furthermore, major challenges and gaps remain: efficacious vaccine, new tools, and expert staff are crucial before CL can be definitively controlled.

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Section: Demographic Risk Factorsmentioning

confidence: 99%

Section: Host Immune Responsesmentioning

confidence: 99%

Determinants of Unresponsiveness to Treatment in Cutaneous Leishmaniasis: A Focus on Anthroponotic Form Due to Leishmania tropica

et al. 2021

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“…Additionally, there was a significant downregulation of TLR2 and TNF-α expression and upregulation of TLR9 expression in isolates from unresponsive versus responsive individuals. Isolates from the former group also showed a significant increase in the level of arginase in monocytes stimulated with L. tropica and cultured promastigotes [6].…”

Section: Tlrs In the Outcome Of Disease 71 Leishmaniasismentioning

confidence: 91%

“…For instance, localized cutaneous leishmaniasis is characterized by ulcers at the site of parasite inoculation, while parasites in diffuse cutaneous leishmaniasis spread throughout the skin and form disfiguring nodules [5]. In Iran, cutaneous leishmaniasis is endemic in 18 of 31 provinces, and approximately one-fifth of the cases belong to anthroponotic cutaneous leishmaniasis, stemming from L. tropica [6]. L. panamensis, a member of the Viannia subgenus of Leishmania, is known to provoke mucosal leishmaniasis.…”

Section: Leishmania Sppmentioning

confidence: 99%

TLR-Mediated Host Immune Response to Parasitic Infectious Diseases

Aguirre-Garcı́a¹,

Rojas-Bernabé²,

Gómez-García³

et al. 2020

Toll-Like Receptors

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Toll-like receptors (TLRs) are important for the host immune response to a variety of pathogens, including bacteria, viruses, fungi, and parasites. These receptors become activated upon recognizing pathogen-associated molecular patterns (PAMPs) and thus initiate the innate immune response to the corresponding pathogen. A key aspect of TLRs is their activation of signaling that leads to cytokine production and an inflammatory response. Additionally, TLRs act as the bridge between innate and acquired immunity, enhancing phagocytosis and the process of killing parasites. We herein focus on how parasites (protozoans and helminths) and their derived products have the capability of stimulating or evading the host response by triggering or inhibiting TLR activation. Parasites often develop successful survival strategies that imply interference with the host immune response. Accordingly, many of these organisms have molecules that modulate inflammation and other aspects of host immunity. Taking advantage of such mechanisms, there are some anti-inflammatory therapies based on human infection with helminths. Helminths and protozoans influence the activity of various TLRs, especially TLR2, TLR4, and TLR9. A better understanding of the role of TLRs and their parasite-derived ligands should certainly provide new therapeutic tools for combatting various parasitic and inflammatory diseases.

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“…However, resistance against SbV has been significantly increased. [7][8][9] For the past few decades, MA has been the drug of choice for the treatment of CL. 10 Although this drug has been the first-line therapy, varying reports of unresponsive patients (10% -59%) with CL have been documented in Iran including Kerman, 10 Bam, [11][12][13] Mashhad, 14 Fars, 15 and Yazd.…”

Section: F I G U R Ementioning

confidence: 99%

The potential therapeutic role of PTR1 gene in non‐healing anthroponotic cutaneous leishmaniasis due to Leishmania tropica

Sezavar

Sharifi

Almani

et al. 2020

Clinical Laboratory Analysis

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Background: Drug resistance is a common phenomenon frequently observed in countries where leishmaniasis is endemic. Due to the production of the pteridine reductase enzyme (PTR1), drugs lose their efficacy, and consequently, the patient becomes unresponsive to treatment. This study aimed to compare the in vitro effect of meglumine antimoniate (MA) on non-healing Leishmania tropica isolates and on MA transfected non-healing one to PTR1. Methods: Two non-healing and one healing isolates of L. tropica were collected from patients who received two courses or one cycle of intralesional MA along with biweekly liquid nitrogen cryotherapy or systemic treatment alone, respectively. After confirmation of L. tropica isolates by polymerase chain reaction (PCR), the recombinant plasmid pcDNA-rPTR (antisense) was transfected via electroporation and cultured on M199. Isolates in form of promastigotes were treated with different concentrations of MA and read using an enzyme-linked immunosorbent assay (ELISA) reader and the half inhibitory concentration (IC 50) value was calculated. The amastigotes were grown in mouse macrophages and were similarly treated with various concentrations of MA. The culture glass slides were stained, and the mean number of intramacrophage amastigotes and infected macrophages were assessed in triplicate for both stages. Results: All three transfected isolates displayed a reduction in optical density compared with the promastigotes in respective isolates, although there was no significant difference between non-healing and healing isolates. In contrast, in the clinical form (amastigotes), there was a significant difference between non-healing and healing isolates (p < 0.05). Conclusion: The results indicated that the PTR1 gene reduced the efficacy of the drug, and its inhibition by antisense and could improve the treatment of non-healing cases. These findings have future implications in the prophylactic and therapeutic modality of non-healing Leishmania isolates to drug. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Differential expression of TLRs 2, 4, 9, iNOS and TNF-α and arginase activity in peripheral blood monocytes from glucantime unresponsive and responsive patients with anthroponotic cutaneous leishmaniasis caused by Leishmania tropica

Cited by 16 publications

References 53 publications

Determinants of Unresponsiveness to Treatment in Cutaneous Leishmaniasis: A Focus on Anthroponotic Form Due to Leishmania tropica

Determinants of Unresponsiveness to Treatment in Cutaneous Leishmaniasis: A Focus on Anthroponotic Form Due to Leishmania tropica

TLR-Mediated Host Immune Response to Parasitic Infectious Diseases

The potential therapeutic role of PTR1 gene in non‐healing anthroponotic cutaneous leishmaniasis due to Leishmania tropica

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