Publisher Correction: Leishmania RNA virus exacerbates Leishmaniasis by subverting innate immunity via TLR3-mediated NLRP3 inflammasome inhibition

Carvalho, Roberto Gameiro de; Lima-Júnior, Djalma S.; Silva, Marcus Vinícius G. da; Dilucca, Marisa; Rodrigues, Tamara Silva; Horta, Catarina V.; Silva, Alexandre L. N.; Frantz, Fabiani Gai; Lorenzon, Lucas Bigolin; Almeida, Fausto; Cantanhêde, Lilian Motta; Ferreira, Ricardo de Godoi Mattos; Cruz, Ângela K.; Zamboni, Dario S.

doi:10.1038/s41467-019-13900-0

Cited by 7 publications

(5 citation statements)

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“…Recent research also explored the role of the NLRP3 inflammasome in the protective effects of Giardia during co-infections. The NLRP3 inflammasome is activated by other protozoan parasites such as Leishmania spp., Plasmodium spp., Entamoeba spp., Naegleria spp., Trypanosoma cruzi , and Toxoplasma gondii ( Mortimer et al, 2014 , 2015 ; Kim et al, 2016 ; de Carvalho et al, 2020 ). New findings now demonstrate that upregulation of mucosal AMPs and reduction of C. rodentium -induced colitis in mice co-infected with Giardia and C. rodentium is mediated by the activation of the NLRP3 inflammasome pathway ( Manko-Prykhoda et al, 2020 ).…”

Section: Giardiasis In Co-infections: a Double-edged Swordmentioning

confidence: 99%

Giardia spp. and the Gut Microbiota: Dangerous Liaisons

et al. 2021

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Alteration of the intestinal microbiome by enteropathogens is commonly associated with gastrointestinal diseases and disorders and has far-reaching consequences for overall health. Significant advances have been made in understanding the role of microbial dysbiosis during intestinal infections, including infection with the protozoan parasite Giardia duodenalis, one of the most prevalent gut protozoa. Altered species composition and diversity, functional changes in the commensal microbiota, and changes to intestinal bacterial biofilm structure have all been demonstrated during the course of Giardia infection and have been implicated in Giardia pathogenesis. Conversely, the gut microbiota has been found to regulate parasite colonization and establishment and plays a critical role in immune modulation during mono and polymicrobial infections. These disruptions to the commensal microbiome may contribute to a number of acute, chronic, and post-infectious clinical manifestations of giardiasis and may account for variations in disease presentation within and between infected populations. This review discusses recent advances in characterizing Giardia-induced bacterial dysbiosis in the gut and the roles of dysbiosis in Giardia pathogenesis.

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Section: Giardiasis In Co-infections: a Double-edged Swordmentioning

confidence: 99%

Giardia spp. and the Gut Microbiota: Dangerous Liaisons

et al. 2021

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“…The consequences of the last event are related to a more acute form of the disease and also resistance to chemotherapy. The effect of LRV1 on immune response is via toll-like receptor 3 (TLR3) and activation of proinflammatory factors and chemokines and therefore increases tissue damages [29]. In the present study, the TF isolates showed no infection with LRV1 but two TF isolates showed to be infected with LRV2, suggesting that other mechanisms might be related to TF.…”

Section: Discussionmentioning

confidence: 49%

Relationship of Leishmania RNA Virus (LRV) and treatment failure in clinical isolates of Leishmania major

et al. 2020

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Objective: Leishmaniasis is caused by different Leishmania spp. Treatment failure (TF) of cutaneous leishmaniasis (CL) is a serious issue that may be due to various reasons, previous studies suggested Leishmania RNA virus (LRV) as a potential cause of TF. Two variant groups of LRV1 and LRV2 are reported. In this study, the presence of LRV1/LRV2 was compared in TF with treatment response (TR) isolates of L. major. Clinical isolates of 15 TF and 15 TR were collected from CL patients referred to the Health Centers of Isfahan. Genomic DNA was extracted to identify Leishmania spp. using ITS1-PCR-RFLP. Identification of LRV1/LRV2 was performed using SYBR Green Real-Time PCR. The statistical analysis to test relationship between the treatment response with Glucantime and the presence of LRV were performed using SPSS 16.0 with Fisher's Exact test. P value of less than 0.05 was considered significant.Results: ITS1-PCR-RFLP results showed that every isolate was identified as L. major. The results showed no LRV1 in any of the samples but 7 TR isolates and 2 TF isolates showed positive for LRV2. Statistical analysis showed no significant difference between the presence of LRV2 and response to Glucantime (p-value = 0.1086). Therefore, other mechanisms might be responsible for TF.

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“…The inhibitory activity of autophagy in inflammasome activation has been previously reported ( 25 ) and may participate in the inhibitory effects of NIC on NLRP3 inflammasome activation in macrophages. A previous report, not consistent with our data, suggested that NIC might function as an NLRP3 activator ( 49 ).…”

Section: Discussionmentioning

confidence: 63%

“…Next, we investigated the mechanisms by which NIC promotes inhibition of the inflammasome activation. NIC is able to trigger autophagy, a cell intrinsic mechanism that reduces the activation of the inflammasome ( 25 – 29 ). Thus, we initially tested whether NIC treatment is able to induce autophagy in macrophages by assessing the conversion of LC3-I to LC3-II, a biomarker of autophagy, by Western blot ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Identification of immunomodulatory drugs that inhibit multiple inflammasomes and impair SARS-CoV-2 infection

et al. 2022

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces mild or asymptomatic COVID-19 in most cases, but some patients develop an excessive inflammatory process that can be fatal. As the NLRP3 inflammasome and additional inflammasomes are implicated in disease aggravation, drug repositioning to target inflammasomes emerges as a strategy to treat COVID-19. Here, we performed a high-throughput screening using a 2560 small-molecule compound library and identified FDA-approved drugs that function as pan-inflammasome inhibitors. Our best hit, niclosamide (NIC), effectively inhibits both inflammasome activation and SARS-CoV-2 replication. Mechanistically, induction of autophagy by NIC partially accounts for inhibition of NLRP3 and AIM2 inflammasomes, but NIC-mediated inhibition of NAIP/NLRC4 inflammasome are autophagy independent. NIC potently inhibited inflammasome activation in human monocytes infected in vitro, in PBMCs from patients with COVID-19, and in vivo in a mouse model of SARS-CoV-2 infection. This study provides relevant information regarding the immunomodulatory functions of this promising drug for COVID-19 treatment.

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Publisher Correction: Leishmania RNA virus exacerbates Leishmaniasis by subverting innate immunity via TLR3-mediated NLRP3 inflammasome inhibition

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cited by 7 publications

References 0 publications

Giardia spp. and the Gut Microbiota: Dangerous Liaisons

Giardia spp. and the Gut Microbiota: Dangerous Liaisons

Relationship of Leishmania RNA Virus (LRV) and treatment failure in clinical isolates of Leishmania major

Identification of immunomodulatory drugs that inhibit multiple inflammasomes and impair SARS-CoV-2 infection

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