Repeated Exposition to Mercury (II) Chloride Enhances Susceptibility to S. schenckii sensu stricto Infection in Mice

Batista-Duharte, Alexander; Téllez-Martínez, Damiana; Jellmayer, Juliana Aparecida; Fuentes, Deivys Leandro Portuondo; Polesi, Marisa Campos; Baviera, Amanda Martins; Carlos, Iracilda Zeppone

doi:10.3390/jof4020064

Cited by 17 publications

(22 citation statements)

References 61 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%

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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%

“…A recent study of our group revealed that mice exposed to mercury (II) chloride enhances susceptibility to S. schenckii sensu stricto infection (Batista-Duharte et al ., 2018). However, there are not studies on the effects of chemicals pollutants on Sporothrix spp biology (Téllez et al ., 2014; Ramírez-Soto et al ., 2018).…”

Section: Introductionmentioning

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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“…After inoculation, several mechanisms of the innate immunity are activated to control the infection directly and by stimulating the specific immune response (Carlos et al, 1994;Gonçalves et al, 2015;Ferreira et al, 2015;Maia et al, 2016;Jellmayer et al, 2017). The importance of these immune mechanisms for the control of S. schenckii-infection is evidenced by the higher fungal colonization and dissemination in immunosuppressed mouse models (Manente et al, 2018;Batista-Duharte et al, 2018a) and immunocompromised patients, mainly individuals with HIV-AIDS (Moreira et al, 2015).…”

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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“…Cytokines were measured using the mouse Th1/Th2/Th17 cytokine cytometric bead array (CBA) kit (BD Biosciences), according to the manufacturer’s instructions using a FACS LRS II Fortessa flow cytometer (BD Biosciences). The data were analyzed using FlowJo (Tree Star, Ashland, OR, USA), and the results of cytokine concentration were expressed in pg/mL [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

Sporothrix schenckii Cell Wall Proteins-Stimulated BMDCs Are Able to Induce a Th1-Prone Cytokine Profile In Vitro

Quinello

Ferreira

Picolli

et al. 2018

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Sporotrichosis is a subcutaneous mycosis affecting humans and other animals. The disease can be acquired by accidental inoculation of the fungus through the skin or through the respiratory system. Sporotrichosis can also be transmitted through bites or scratches by infected cats and more rarely by other animals (zoonotic transmission). Conventional antifungal therapy is especially inefficient in immunocompromised patients, who tend to develop the most severe forms of the disease, thus prompting the search for alternative therapies. Given their antigen-presenting properties, dendritic cells (DCs) have been used in both prophylactic and therapeutic vaccination strategies. Hence, this study aims to assess the use of DCs as a prophylactic tool in sporotrichosis by evaluating the immune profile induced by Sporothrix schenckii cell wall proteins (SsCWP)-stimulated, bone-marrow-derived DCs (BMDCs). Mouse BMDCs were stimulated with SsCWP for 24 h and analyzed for the surface expression of costimulatory molecules and TLR-4, as well as for the secretion of proinflammatory cytokines and IL-10. Following that, activated BMDCs were cocultured with splenocytes for 72 h and had the same cytokines measured in the supernatant. SsCWP-stimulated BMDCs showed higher expression of CD80, CD86, and CD40, but not TLR-4, and higher secretion of IL-6, IL-17A, and TNF. On the other hand, higher levels of IFN-γ, IL-10, and IL-2 were found in the supernatants of the coculture as compared with the BMDCs alone; TNF secretion was almost completely abrogated, whereas IL-6 was only partially inhibited and IL-17A was unaffected. Our results thus suggest that SsCWP-stimulated BMDCs are able to induce a Th1-prone cytokine profile which is known to be protective against other fungal diseases. This result could lead to studies which evaluate the development of prophylactic and/or therapeutic DC-based tools against sporotrichosis.

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Repeated Exposition to Mercury (II) Chloride Enhances Susceptibility to S. schenckii sensu stricto Infection in Mice

Cited by 17 publications

References 61 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

Sporothrix schenckii Cell Wall Proteins-Stimulated BMDCs Are Able to Induce a Th1-Prone Cytokine Profile In Vitro

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