Paracoccidioides brasiliensis induces IL-32 and is controlled by IL-15/IL-32/vitamin D pathway in vitro

Matos, Grazzielle Guimarães de; Figueiredo, Ana Marina Barroso de; Gonçalves, Pedro Hugo Diniz; Silva, Lucas Luiz de Lima; Bastista, Aline Carvalho; Borges, Clayton Luiz; Soares, Célia Maria de Almeida; Joosten, Leo A. B.; Ribeiro‐Dias, Fátima

doi:10.1016/j.micpath.2021.104864

Cited by 3 publications

(6 citation statements)

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“…Cha et al [77] demonstrated that vitamin A deficiency in a murine model impairs the differentiation of T cells towards a Th17 profile, reducing the expression of cytokines as IL-22. Our group has also recently demonstrated that vitamin D can improve the fungicidal activity of PBMCs infected with P. brasiliensis [20]. There are only two studies about P. brasiliensis infection and IL-22.…”

Section: Discussionmentioning

confidence: 99%

“…For inhibition of downstream signalling pathways molecules, the cells were treated with 1 µM of Raf-1 (GW5074, Sigma-Aldrich) and 50 nM of Syk inhibitor (574711, EMD-Millipore, Burlington, MA, USA). PBMCs were stimulated with heat-killed yeast cells of P. brasiliensis (2.5 PBMCs: 1 yeast cell), particulated Pb18 antigens (20 µg/mL; prepared as in Guimarães de Matos et al [20]), LPS (100 ng/mL, E. coli 011:B4, Sigma-Aldrich) or Zymosan (50 µg/mL; Sigma-Aldrich). The cell culture was incubated for 24 h at 37 • C. After incubation, the supernatant was collected to measure IL-1β by immunoenzymatic assay (ELISA), using a commercial kit according to the instructions of manufacturer (BD or R&D Systems).…”

Section: Functional Validation Of Potential Causal Genes (Clec7a Prom1)mentioning

confidence: 99%

“…In turn, human monocytes from healthy individuals exposed to viable yeasts of P. brasiliensis produced IL-1β, IL-6, IL-10 and TNF [19]. Sonicated P. brasiliensis also induces IL-32 production in PBMCs from healthy individuals, a cytokine associated with the monocyte capacity to control the fungus [20]. Moreover, PBMCs from individuals cured of PCM, stimulated ex vivo with the P. brasiliensis gp43 protein, produced increased levels of IL-2, IFNγ and IL-10; however, PBMCs from patients with active PCM (chronic or acute form) produced low levels of IL-2 and IFNγ with substantial amounts of IL-10 in response to stimulation with gp43 [21].…”

Section: Introductionmentioning

confidence: 97%

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Genome-Wide Association Study Reveals CLEC7A and PROM1 as Potential Regulators of Paracoccidioides brasiliensis-Induction of Cytokine Production in Peripheral Blood Mononuclear Cells

Figueiredo

Santos

Kischkel

et al. 2023

JoF

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Paracoccidioidomycosis (PCM) is a systemic mycosis caused by fungi of the genus Paracoccidioides and the different clinical forms of the disease are associated with the host immune responses. Quantitative trait loci mapping analysis was performed to assess genetic variants associated with mononuclear-cells-derived cytokines induced by P. brasiliensis on 158 individuals. We identified the rs11053595 SNP, which is present in the CLEC7A gene (encodes the Dectin-1 receptor) and the rs62290169 SNP located in the PROM1 gene (encodes CD133) associated with the production of IL-1β and IL-22, respectively. Functionally, the blockade of the dectin-1 receptor abolished the IL-1β production in P. brasiliensis-stimulated PBMCs. Moreover, the rs62290169-GG genotype was associated with higher frequency of CD38+ Th1 cells in PBMCs cultured with P. brasiliensis yeasts. Therefore, our research indicates that the CLEC7A and PROM1 genes are important for the cytokine response induced by P. brasiliensis and may influence the Paracoccidioidomycosis disease outcome.

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Section: Discussionmentioning

confidence: 99%

Section: Functional Validation Of Potential Causal Genes (Clec7a Prom1)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Genome-Wide Association Study Reveals CLEC7A and PROM1 as Potential Regulators of Paracoccidioides brasiliensis-Induction of Cytokine Production in Peripheral Blood Mononuclear Cells

Figueiredo

Santos

Kischkel

et al. 2023

JoF

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“…Pro-inflammatory cytokines such as (TNF- α ; 19), IL-12 ( 1 ), IL-18 ( 4 ), and IL-1 β ( 36 ) induce IL-32 production. IL-32 is also expressed in viral ( 37 – 39 ), bacterial ( 40 , 41 ), fungal ( 42 ), and protozoan infections ( 9 ). Pathogen-associated molecular patterns, such as lipopolysaccharide (LPS), muramyl dipeptide (MDP), RNA analog Poly (I:C), and oxidative stress, also induce IL-32 ( 21 , 26 , 43 , 44 ).…”

Section: Biology Of Il-32mentioning

confidence: 99%

“…L. braziliensis infection in human monocyte-derived macrophages was reportedly best controlled when the culture medium contained IL-32γ and a sufficient amount of vitamin D ( Figure 1D ) ( 15 ). However, this pathway appears important in the control of various microorganisms in human macrophages as the IL-32–vitamin D axis is also crucial for controlling the growth of Paracoccidioides brasiliensis , a fungus that causes paracoccidioidomycosis ( 42 ).…”

Section: Il-32 In Different Leishmaniasesmentioning

confidence: 99%

A Critical Overview of Interleukin 32 in Leishmaniases

Ribeiro‐Dias

Oliveira

2022

Front. Immunol.

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Interleukin-32 (IL-32) has several immune regulatory properties, which have driven its investigation in the context of various diseases. IL-32 expression is reported to be induced in the lesions of patients with American tegumentary leishmaniasis (ATL) by the New World Leishmania spp. that are responsible for causing ATL and visceral leishmaniasis (VL). IL-32 expression may elevate the inflammatory process through the induction of pro-inflammatory cytokines and also via mechanisms directed to kill the parasites. The genetic variants of IL-32 might be associated with the resistance or susceptibility to ATL, while different isoforms of IL-32 could be associated with distinct T helper lymphocyte profiles. IL-32 also determines the transcriptional profile in the bone marrow progenitor cells to mediate the trained immunity induced by β-glucan and BCG, thereby contributing to the resistance against Leishmania. IL-32γ is essential for the vitamin D-dependent microbicidal pathway for parasite control. In this context, the present review report briefly discusses the data retrieved from the studies conducted on IL-32 in leishmaniasis in humans and mice to highlight the current challenges to understanding the role of IL-32 in leishmaniasis.

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Transcriptome Analysis of Co-Cultures of THP-1 Human Macrophages with Inactivated Germinated Trichophyton rubrum Conidia

Cantelli

Segura

Bitencourt

et al. 2023

JoF

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Although most mycoses are superficial, the dermatophyte Trichophyton rubrum can cause systemic infections in patients with a weakened immune system, resulting in serious and deep lesions. The aim of this study was to analyze the transcriptome of a human monocyte/macrophage cell line (THP-1) co-cultured with inactivated germinated T. rubrum conidia (IGC) in order to characterize deep infection. Analysis of macrophage viability by lactate dehydrogenase quantification showed the activation of the immune system after 24 h of contact with live germinated T. rubrum conidia (LGC). After standardization of the co-culture conditions, the release of the interleukins TNF-α, IL-8, and IL-12 was quantified. The greater release of IL-12 was observed during co-culturing of THP-1 with IGC, while there was no change in the other cytokines. Next-generation sequencing of the response to T. rubrum IGC identified the modulation of 83 genes; of these, 65 were induced and 18 were repressed. The categorization of the modulated genes showed their involvement in signal transduction, cell communication, and immune response pathways. In total, 16 genes were selected for validation and Pearson’s correlation coefficient was 0.98, indicating a high correlation between RNA-seq and qPCR. Modulation of the expression of all genes was similar for LGC and IGC co-culture; however, the fold-change values were higher for LGC. Due to the high expression of the IL-32 gene in RNA-seq, we quantified this interleukin and observed an increased release in co-culture with T. rubrum. In conclusion, the macrophages-T. rubrum co-culture model revealed the ability of these cells to modulate the immune response, as demonstrated by the release of proinflammatory cytokines and the RNA-seq gene expression profile. The results obtained permit to identify possible molecular targets that are modulated in macrophages and that could be explored in antifungal therapies involving the activation of the immune system.

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Paracoccidioides brasiliensis induces IL-32 and is controlled by IL-15/IL-32/vitamin D pathway in vitro

Cited by 3 publications

References 60 publications

Genome-Wide Association Study Reveals CLEC7A and PROM1 as Potential Regulators of Paracoccidioides brasiliensis-Induction of Cytokine Production in Peripheral Blood Mononuclear Cells

Genome-Wide Association Study Reveals CLEC7A and PROM1 as Potential Regulators of Paracoccidioides brasiliensis-Induction of Cytokine Production in Peripheral Blood Mononuclear Cells

A Critical Overview of Interleukin 32 in Leishmaniases

Transcriptome Analysis of Co-Cultures of THP-1 Human Macrophages with Inactivated Germinated Trichophyton rubrum Conidia

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