<i>Mycobacterium leprae</i>induces a tolerogenic profile in monocyte-derived dendritic cells via TLR2 induction of IDO

Oliveira, Jéssica A. P.; Gandini, Mariana; Sales, Jorgenilce S.; Fujimori, Sérgio K.; Barbosa, Mayara G. M.; Frutuoso, Valber S.; Moraes, Milton Ozório; Sarno, Euzenir Nunes; Pessolani, Maria Cristina Vidal; Pinheiro, Roberta Olmo

doi:10.1002/jlb.4a0320-188r

Cited by 7 publications

(7 citation statements)

References 36 publications

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“…In addition to Dectin-1, TLR2, another PPR, has been shown to affect IDO-1 production. For instance, a study has shown that fractions from Mycobacterium leprae modulated IDO-1 production by monocyte-derived DCs in a TLR2-dependent manner 21 . Considering this and prior research indicating a role for TLR2 in the activity of MDSCs 26 , 27 , we aimed to investigate the impact of TLR2 signaling on IDO-1 expression by MDSCs challenged with P. brasiliensis yeasts in vitro.…”

Section: Resultsmentioning

confidence: 99%

“…The expression of IDO-1 is a major mechanism of immunosuppression in a variety of cancer types 18 , and the infiltration of MDSCs has been associated with this enzyme activity 19 . Furthermore, in different pathological contexts the expression of IDO-1 was already shown to be induced by pattern recognition receptors (PRRs), such as Dectin-1 20 , Toll-like receptor 2 (TLR2) 21 , and TLR4 22 . Moreover, these PPRs are involved in the activity or recruitment of MDSCs in several infectious diseases 15 , 23 , 24 .…”

Section: Introductionmentioning

confidence: 99%

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The immunosuppressive activity of myeloid-derived suppressor cells in murine Paracoccidioidomycosis relies on Indoleamine 2,3-dioxygenase activity and Dectin-1 and TLRs signaling

Kaminski,

Preite,

Borges

et al. 2023

Sci Rep

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Paracoccidioidomycosis (PCM) is a systemic mycosis with a high incidence in Latin America. Prior studies have demonstrated the significance of the enzyme Indoleamine 2,3-dioxygenase (IDO-1) in the immune regulation of PCM as well as the vital role of myeloid-derived suppressor cells (MDSCs) in moderating PCM severity. Additionally, Dectin-1 and Toll-Like Receptors (TLRs) signaling in cancer, infection, and autoimmune diseases have been shown to impact MDSC-IDO-1+ activity. To expand our understanding of MDSCs and the role of IDO-1 and pattern recognition receptors (PRRs) signaling in PCM, we generated MDSCs in vitro and administered an IDO-1 inhibitor before challenging the cells with Paracoccidioides brasiliensis yeasts. By co-culturing MDSCs with lymphocytes, we assessed T-cell proliferation to examine the influence of IDO-1 on MDSC activity. Moreover, we utilized specific antibodies and MDSCs from Dectin-1, TLR4, and TLR2 knockout mice to evaluate the effect of these PRRs on IDO-1 production by MDSCs. We confirmed the importance of these in vitro findings by assessing MDSC-IDO-1+ in the lungs of mice following the fungal infection. Taken together, our data show that IDO-1 expression by MDSCs is crucial for the control of T-cell proliferation, and the production of this enzyme is partially dependent on Dectin-1, TLR2, and TLR4 signaling during murine PCM.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The immunosuppressive activity of myeloid-derived suppressor cells in murine Paracoccidioidomycosis relies on Indoleamine 2,3-dioxygenase activity and Dectin-1 and TLRs signaling

Kaminski,

Preite,

Borges

et al. 2023

Sci Rep

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“…The target gene IDO1 of novel_973 encodes an intracellular enzyme that catalyzes the early stage of tryptophan catabolism along the kynurenine pathway. IDO-1 affects immunity through two nonexclusive mechanisms: establishment of a local response with amino acid deprivation, which inhibits pathogen growth, and production of tryptophan metabolites with immunomodulatory functions or cytotoxic agents that inhibit T-cell activation and modulate differentiation of naive T cells into regulatory T cells ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Three Novel miRNAs in the Lymph Nodes of Sheep Immunized With the Brucella suis Strain 2 Vaccine

et al. 2022

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Ovine and caprine brucellosis, both caused by Brucella melitensis, lead to substantial economic losses in the animal industry and health problems in human populations. Brucella suis strain 2 (B.suis S2), as a live attenuated vaccine, is used extensively in China to prevent brucellosis. It has been proven that microRNA (miRNAs) are involved in the immunopathogenesis of brucellosis; however, the miRNA-driven mechanism of immune response to B.suis S2 in vivo remains unknown. To determine which new miRNAs are involved in the host immune response to B.suis S2 and elucidate the function of these miRNAs, we performed a comprehensive analysis of miRNA expression profiles in sheep immunized with B.suis S2 using the high-throughput sequencing approach. The submandibular lymphatic nodes from sheep seropositive for Brucella were collected at 7, 14, 21, 30, 60 and 90 days post-immunization. MiRNA sequencing analysis revealed that 282 differentially expressed miRNAs (|log2 fold-change |>0.5 and p < 0.05) were significantly enriched in the immune pathways, including the NF-kappa B signaling pathway, B cell receptor signaling pathway, p53 signaling pathway and complement and coagulation cascades. Increasing the threshold to |log2 fold change|>1 and p < 0.01 revealed 48 differentially expressed miRNAs, 31 of which were novel miRNAs. Thirteen of these novel miRNAs, which were differentially expressed for at least two time points, were detected via RT-qPCR assays. The novel_229, novel_609, novel_973 and oar-miR-181a assessed by RT-qPCR were detectable and consistent with the expression patterns obtained by miRNA sequencing. Functional analyses of these miRNAs demonstrated that their target genes participated in the immune response pathways, including the innate and adaptive immunity pathways. The immune-related target genes of novel_229 included ENSOARG00000000649 and TMED1, as well as LCN2, PDPK1 and LPO were novel_609 target genes. The immune-related target genes of novel_973 included C6orf58, SPPL3, BPIFB1, ENSOARG00000021083, MPTX1, CCL28, FGB, IDO1, OLR1 and ENSOARG00000020393. The immune-related target genes of oar-miR-181a included ENSOARG00000002722, ARHGEF2, MFAP4 and DOK2. These results will deepen our understanding of the host miRNA-driven defense mechanism in sheep immunized with B.suis S2 vaccine, and provide the valuable information for optimizing vaccines and developing molecular diagnostic targets.

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“…The literature has provided us with some evidence indicating a strong relationship between host cell metabolism and the inflammatory response against M. leprae , and how they can influence each other ( de Macedo et al, 2020 ; Oliveira J. A. P. et al, 2021 ).…”

Section: Host–cell Interaction In the Context Of Leprosy Neuropathymentioning

confidence: 99%

“…While the membrane fraction of M. leprae induced the production of pro-inflammatory cytokines TNF and IL-6, the soluble fraction induced an increase in IL-10 in mDCs. The co-culture of mDCs with autologous lymphocytes induced an increase in regulatory T cell (Treg) frequency in MLSA-stimulated cultures, showing that M. leprae constituents may play opposite roles that could possibly be related to the dubious effect of IDO1 in the different clinical forms of disease ( Oliveira J. A. P. et al, 2021 ).…”

Section: Kynurenines In Leprosy Pathogenesismentioning

confidence: 99%

Kynurenines in the Pathogenesis of Peripheral Neuropathy During Leprosy and COVID-19

Oliveira

Athaide

RAHMAN

et al. 2022

Front. Cell. Infect. Microbiol.

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Inflammatory disorders are associated with the activation of tryptophan (TRYP) catabolism via the kynurenine pathway (KP). Several reports have demonstrated the role of KP in the immunopathophysiology of both leprosy and coronavirus disease 19 (COVID-19). The nervous system can be affected in infections caused by both Mycobacterium leprae and SARS-CoV-2, but the mechanisms involved in the peripheral neural damage induced by these infectious agents are not fully understood. In recent years KP has received greater attention due the importance of kynurenine metabolites in infectious diseases, immune dysfunction and nervous system disorders. In this review, we discuss how modulation of the KP may aid in controlling the damage to peripheral nerves and the effects of KP activation on neural damage during leprosy or COVID-19 individually and we speculate its role during co-infection.

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Mycobacterium lepraeinduces a tolerogenic profile in monocyte-derived dendritic cells via TLR2 induction of IDO

Cited by 7 publications

References 36 publications

The immunosuppressive activity of myeloid-derived suppressor cells in murine Paracoccidioidomycosis relies on Indoleamine 2,3-dioxygenase activity and Dectin-1 and TLRs signaling

The immunosuppressive activity of myeloid-derived suppressor cells in murine Paracoccidioidomycosis relies on Indoleamine 2,3-dioxygenase activity and Dectin-1 and TLRs signaling

Downregulation of Three Novel miRNAs in the Lymph Nodes of Sheep Immunized With the Brucella suis Strain 2 Vaccine

Kynurenines in the Pathogenesis of Peripheral Neuropathy During Leprosy and COVID-19

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