The <scp>NLRP</scp>3 inflammasome contributes to host protection during <i>Sporothrix schenckii</i> infection

Gonçalves, Amanda; Ferreira, Lucas Souza; Manente, Francine Alessandra; Faria, Carolina Maria Quinello Gomes de; Polesi, Marisa Campos; Andrade, Cléverton Roberto de; Zamboni, Dario S.; Carlos, Iracilda Zeppone

doi:10.1111/imm.12719

Cited by 52 publications

(41 citation statements)

References 74 publications

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“…A greater response of all these mediators was observed in the animals infected with the treated fungi, principally those that grew at the highest concentration of toluene (Fig 4). Several studies reveals that a Th1 and Th17 are stimulated during S. schenckii infection and they are important for the fungal clearance (Ferreira et al ., 2015; Gonçalves et al ., 2017; Batista-Duharte et al ., 2018). Interestingly, a recent report of our group reveled that both S. schenckii and the more virulent S. brasiliensis stimulate similar Th1 response, but S. brasiliensis induced a more severe disease associated with sustained Th17 and a regulatory T cells (Tregs) responses than S. schenckii (Batista-Duharte et al ., 2018).…”

Section: Resultsmentioning

confidence: 99%

Adaptive stress response induced by toluene increasesSporothrix schenckiivirulence and host immune response

Téllez-Martínez

Batista-Duharte

Silva

et al. 2019

Preprint

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24Environmental factors modify the physiology of microorganisms, allowing their survival in 25 extreme conditions. However, the influence of chemical contaminants on fungal virulence has 26 been little studied. Sporotrichosis is an emergent fungal disease caused by Sporothrix schenckii, 27 a soil-inhabiting fungus that has been found in polluted environments. Here, we evaluated the 28 adaptive stress response of S. schenckii induced by toluene, a key soil contaminant. The effect 29 on fungal virulence and host immune response was also assessed. The fungus survived up to 30 0.10% toluene in liquid medium. Greater production of melanosomes and enhanced activity 31 superoxide dismutase, associated to increased tolerance to H2O2 were observed in toluene-32 exposed fungi. Intraperitoneal infection of mice with S. schenckii treated with either 0, 0.01 or 33 0.1% of toluene, resulted in greater fungal burden at day 7 post-infection in spleen and liver in 34 the groups infected with fungus treated with toluene 0.1%. A higher production of Il-1β, TNF-35 α, IL-10 and nitric oxyde by peritoneal macrophages and IFNɣ, IL-4 and IL-17 by splenocytes 36 was also observed in that group. Our findings showed that morphological and functional 37 changes induced by toluene leads to increased S. schenckii virulence and antifungal host 38 immune response in our model. 39 40 41 42 43 44 45 78 Aromatic compounds such as benzene, toluene, ethylbenzene and xylene isomers, 79 collectively known as BTEX, are one of the major contributors to environmental pollution. 80 BTEX are extensively used as solvents in many industrial processes and as base reagents for 81 the production of chemicals products. In addition, BTEX are components of gasoline and 82 aviation fuels. They are often released in the environment during production, transport, use and 83 disposal, causing groundwater, surface water, and soil contamination. Toluene has been found 84 in at least 1,012 of the 1,699 National Priorities List sites identified by the Environmental 85 Protection Agency (EPA) and it is included in the Agency for Toxic Substances and Disease 86 Registry (ATSDR) 2017 substance priority list, which is based on a combination of their 87 frequency, toxicity, and potential for human exposure (Agency for Toxic Substances and 88 Disease Registry. ATSDR's Substance Priority List. 2017).89Prenafreta-Boldu isolated several fungi, including S. schenckii, in biofilters exposed to 90 polluted air or hydrocarbon gas streams. The data from this research showed that volatile 91 hydrocarbon-degrading strains are closely related to a very restricted number of pathogenic 92 fungal species that cause severe mycoses, especially neurological infections, in 93 immunocompetent individuals (Prenafeta-Boldú et al., 2006). 94To date, there have been no studies examining the influence of chemical contaminants 95 on the biology of S. schenckii sensu latu. Given that this fungus inhabits soils and this niche is 96 frequently contaminated with oil and their products, the objective of this...

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Section: Resultsmentioning

confidence: 99%

Adaptive stress response induced by toluene increasesSporothrix schenckiivirulence and host immune response

Téllez-Martínez

Batista-Duharte

Silva

et al. 2019

Preprint

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“…Differences in immunogenicity between the different clinical isolates of S. schenckii sensu lato and the recognition of several fungal antigens by specific antibodies induced in infected human, cats and rodents have been reported (Fernandes et al, 2013;Della Terra et al, 2017). Moreover, some studies have addressed the role of the cellular-mediated immune response in sporotrichosis by evaluating the T helper immune response induced in vitro or in murine models of systemic S. schenckii sensu stricto infection (Uenotsuchi et al, 2006;Maia et al, 2006;Ferreira et al, 2015;Gonçalves et al, 2017). However, the role of Tregs in sporotrichosis has yet to be determined, and comparative studies of T cells response against different species of S. schenckii sensu lato have not been conducted.…”

Section: Introductionmentioning

confidence: 99%

Sporothrix brasiliensis induces a more severe disease associated with sustained Th17 and regulatory T cells responses than Sporothrix schenckii sensu stricto in mice

et al. 2018

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Little is known about the differences in the CD4þ T-cell response induced by Sporothrix schenckii and Sporothrix brasiliensis, the most virulent species that cause sporotrichosis. Here, the helper (Th) and regulatory T cells (Tregs) responses were evaluated comparatively in a murine model of sporotrichosis on days 7, 21 and 35 after subcutaneous infection with either S. schenckii or S. brasiliensis conidia. The fungal load was measured at the site of infection, as well as in the liver and spleen. The Th1/Th17/Tregs responses were analyzed in the spleen, while the level of IL-2, IL-4, IL-6, TNF-alpha, IFN-ɣ, IL-17A and IL-10 cytokines were measured at the local site of infection on 24 h postinfections and in sera on the indicated days. S. brasiliensis caused a longer-lasting infection in the skin and chronic systemic dissemination associated to more severe granulomatous lesions. Similar Th1/Th1-Th17/Tregs responses were induced by both S. brasiliensis and S. schenckii on 7th and 21st d.p.i but on 35 d.p.i a reduction of Th1 and Th1-Th17 cells, associated to higher values of Th17/Tregs cells was observed only in S. brasiliensis-infected mice. In summary, S. brasiliensis caused a more severe disease associated with sustained Th17/Tregs responses than S. schenckii in mice.

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“…A significant decrease in atherosclerotic lesion size has also observed at the aortic sinus of HFD-fed LDL-R⁻/⁻ mice reconstituted with NLRP3 knockout bone marrow cells [23]. In addition, previous studies have shown that NLRP3 recruits caspase-1, leading to the activation of caspase-1, maturation and secretion of IL-1β and IL-18, and initiation of pyroptosis [24][25][26][27]. Our results showed that the cardiac tissues in the HFD + TQ group expressed markedly reduced levels of NLRP3, caspase-1, IL-1β and IL-18 compared with that in the HFD group, indicating that TQ downregulated HFD-induced pyroptosis.…”

Section: Discussionmentioning

confidence: 89%

Thymoquinone protects against hyperlipemia-induced cardiac damage in low-density lipoprotein receptor-deficient (LDL-R−/−) mice

Pei¹,

Guan²,

Zhu³

et al. 2020

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Background Hyperlipemia is a risk factor for cardiac damage and cardiovascular disease. Several studies have shown that thymoquinone (TQ) can protect against cardiac damage. The aim of this study was to investigate the possible protective effects of TQ against hyperlipemia-induced cardiac damage in low-density lipoprotein receptor deficient (LDL-R−/−) mice. Methods: Eight-week-old male LDL-R−/−mice were randomly divided into the following three groups: the control group fed a normal diet (ND group), the high fat diet (HFD) group, and the HFD mixed with TQ (HFD+TQ) group. All groups were fed the different diets for 8 weeks. Blood samples were obtained from the inferior vena cava, collected in serum tubes, and stored at -80 °C until use. Cardiac tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the cardiac tissues was snap-frozen in liquid nitrogen for mRNA preparation or immunoblotting.Results The levels of metabolism-related factors, such as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-sensitivity C-reactive protein (hs-CRP), were decreased in the HFD+TQ group compared with that in the HFD group. Periodic acid-Schiff staining demonstrated that lipid deposition was lower in the HFD+TQ group than that in the HFD group. The expression of pyroptosis indicators (NOD-like receptor 3 [NLRP3], interleukin [IL]-1β, IL-18 and caspase-1), pro-inflammation factors (IL-6 and tumour necrosis factor alpha [TNF-α]), and macrophage markers (cluster of differentiation [CD]68) was significantly downregulated in the HFD+TQ group compared with that in the HFD group.Conclusions Our results indicate that TQ may serve as a potential therapeutic agent for hyperlipemia-induced cardiac damage.

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The NLRP3 inflammasome contributes to host protection during Sporothrix schenckii infection

Cited by 52 publications

References 74 publications

Adaptive stress response induced by toluene increasesSporothrix schenckiivirulence and host immune response

Adaptive stress response induced by toluene increasesSporothrix schenckiivirulence and host immune response

Sporothrix brasiliensis induces a more severe disease associated with sustained Th17 and regulatory T cells responses than Sporothrix schenckii sensu stricto in mice

Thymoquinone protects against hyperlipemia-induced cardiac damage in low-density lipoprotein receptor-deficient (LDL-R−/−) mice

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