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Species name and common name: Fonsecaea pedrosoi complex which includes F. monophora and the previously named species F. compacta, now. Fonsecaea pedrosoi (Brumpt) Negroni, Rev. Inst. Bact.: () [MB#]. Muriform cells, the parasitic form of Fonsecaea pedrosoi, are highly prevalent in infected tissues, especially in long-standing lesions. In this.

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Immunity to Human Fungal Pathogens: Fonsecaea pedrosoi is the main etiologic agent fonsecqe chromoblastomycosis CBMone of the most prevalent subcutaneous mycosis in tropical and subtropical countries. CBM is a poorly characterized chronic infection that commonly starts after transcutaneous inoculation of conidia and saprophytic hyphae of F. Recently, we have shown that unlike conidia, hyphae and muriform cells pedrosoj parasitic morphotype of F.

We show here that F. Finally, we showed using a murine CBM model that F. Chromoblastomycosis CBM is a chronic, granulomatous, suppurative, and often debilitating cutaneous and subcutaneous mycosis, caused by dimorphic filamentous fungi belonging to the Dematiaceous family 1 — 3.

Multiple dematiaceous fungi are related to the disease etiology; of these, Fonsecaea pedrosoi and Cladophialophora carrionii are the most frequently identified fungal species in human CBM skin lesions. This disease occurs worldwide; however, it is mostly prevalent in tropical and subtropical areas 45.

Clinically, CBM is characterized by the slow development of polymorphic skin lesions, such as nodules, warts, tumors, plaques, and scars, after inoculation of fungal propagules consisting of conidia and hyphal fragments into host skin, more frequently into prdrosoi limbs 6 — 8.

During infection of mammalian host, these primarily saprophyte fungal forms undergo transformation into the intensely melanized and thick-walled muriform sclerotic cells, the parasitic peedrosoi of F. Although little is known about the immune fonaecae of the host to infection by F. In this scenario, the abrogation of ILp35 transcription in human dendritic cells, leading to Th1-deficient development by several Fonsecaea species, and the Thmediated response suppression in experimentally infected mice, suggest that this fungal pathogen evade host immune response by complex pddrosoi.

These mechanisms usually encompass the evasion or subversion of the function of innate pattern recognition receptors PRRs in the detection of conserved fungal components or pathogen-associated molecular patterns PAMPs by phagocytes 10 — A number of PRRs families have been associated with F.

The members of the NLR protein family typically share three functional domains: NLRP3 inflammasome, the most studied and the main inflammasome associated with fungal infection, is activated by a typical two-step mechanism: The activation step is associated with the assembly of the multiprotein complex induced by a broad variety of endogenous danger-associated molecules Pevrosoisuch as potassium efflux, production of reactive oxygen species ROSphagolysosome acidification, and cathepsin B release.

Several conditions may lead to DAMPs production, pedrsooi metabolic disorders, inflammatory diseases, and infections. One aspect associated with inflammasome activation is fungal morphotype diversity and complexity.

Fonsecaea pedrosoi – Wikipédia, a enciclopédia livre

Indeed, we have recently showed that unlike conidia, the hyphae and muriform sclerotic cells of F. In this context, we aimed to evaluate the inflammasome activation by F.

Furthermore, we demonstrated using an experimental CBM model that F.

However, we did not observe an influence of the NLRP3 inflammasome on the control of the fungal infection. In order to obtain purified conidia and fonseccae for experiments, virulent F. A mix of purified hyphae and conidia at a 3: Briefly, bone marrow cells were flushed out of murine femurs and tibias and submitted to erythrocyte lysis using tris-buffered ammonium chloride. On day 3, another 10 mL of fresh complete medium was added to the culture. fonsecaw


On day 6, half of the medium was exchanged. THP-1 cells were maintained and used under the same experimental use conditions.

Bone marrow-derived macrophages derived from wild-type WT or knockout mice were infected with F. In order to induce and evaluate conidial swelling, F. Infected BMDMs were washed to discard nonphagocyted fungus and lysed with 0. Then, fungal were fixed with PFA treatment, washed twice, and evaluated by flow cytometry analysis.

After infection, the cell culture supernatant was harvested for NO determination. The remaining cell monolayers were carefully washed to remove non-adherent cells, lysed as described above, and re-suspended in PBS.

After 24 h of infection with F. Then, cells were washed and samples were analyzed by flow cytometry as described above. Gordon Brown University of Aberdeen, Scotland. Mice were euthanized at 14, 21, and 28 days postinfection and the footpad was collected, weighed, and homogenized for ELISA assay and plated for CFU analysis.

Absorbance was measured at nm using a microplate reader. Results were expressed as cytokines pictogram per milliliters or per mg of tissue, for samples obtained from in vivo assays.

Statistical analysis was conducted using GraphPad Prism v. To determine whether F. To test if the size of conidia could affect the BMDM activation, we induced swollen-conidia Figure S1 in Supplementary Materialan intermediate stage of conidia-into-hyphae transformation, and used it to stimulate BMDMs.

These finding suggest that that the viability of F. Differential inflammasome activation requirements in bone marrow-derived macrophages BMDMs and dendritic cells BMDCs are morphotype-dependent in Fonsecaea pedrosoi infection.

Macrophages play central roles in host immune response against fungal infections Likewise, these phagocytes are not only ubiquitous in CBM lesions but are also actively involved in the recognition of fungal cells and in the modulation of inflammatory responses against F. In this context, we performed subsequent assays focused on macrophage-hyphae interaction, since we show here that hyphae are the F.

To clarify the nature of the PRRs that are involved in the F.

The Syk-NF-kB signaling pathway, coupled to dectin-1, dectin-2, and dectin-3 receptors, enables inflammasome activation by bone marrow-derived macrophages BMDMs challenged with Fonsecaea pedrosoi hyphae. Further, since the inhibition of Syk signaling did not completely abrogate the IL-1B secretion Figure 3 Awe reasoned that an alternative Syk-independent dectinNF-kB signaling pathway would be in use.

The results indicate that the Syk-NF-kB signaling pathway, coupled to dectin-1, dectin-2, and dectin-3 receptors, enables inflammasome activation by BMDMs challenged with F. To assess whether F. In addition to its role in maturing inflammasome-derived cytokines, caspase-1 mediate an inflammasome-dependent cell death mechanism termed pyroptosis, which leads to plasma membrane lysis and release of cytoplasmic content, including lactate dehydrogenase LDH.

Inflammasome activation by Fonsecaea pedrosoi hyphae is dependent on caspase-1 and caspase Thus, we first evaluated the gene transcription of these receptors in BMDMs upon hyphal infection, and only Nlrp3 was upregulated Figure 5 A. Then, cells were infected with F.

NLRP3 is activated in response to a myriad of microbial infections through the sensing of their common-induced cellular disturbances, principally potassium efflux, ROS production, phagolysosomal acidification, and cathepsin B release Altogether, our data show that F. Some studies have demonstrated that inflammasome activation drives host protective immune responses against fungal pathogens, such as C.

We observed no differences in fungal burden among experimental groups Figures 6 A,Ewhich we already expected for infection with conidia, since this morphotype alone is unable to activate the inflammasome in BMDMs, as demonstrated in the present study Figure 2 A.

Therefore, we went further and co-stimulated infected BMDMs with nigericin to promote strong inflammasome activation, as shown in Figure 2 A, and then performed the CFU assay.


Fonsecaea pedrosoi – Wikipedia

Nevertheless, the inducible burst in inflammasome activity was not accompanied by diminished recovery of viable fungus from BMDMs infected with conidia or hyphae Figures 6 B,F. This can be explained in part because F. Inflammasome activation does not promote in vitro fungicidal activity of bone marrow-derived macrophages BMDMs challenged with Fonsecaea pedrosoi conidia or hyphae.

BMDMs were infected for 24 h with F. Then, culture supernatant was collected for nitrite measurement by Griess reagent, whereas infected cells were lysed to perform colony-forming unit CFU analysis.

In order to verify whether F. In addition, we observed significant levels of IL only in an advanced stage of remission of the disease, at 28 d.

Fonsecaea pedrosoi

Histological examination of infected tissues from all groups show similar features fonsceae indicated by the presence of exudative areas and inflammatory infiltrates early as 14 d. Consistently with CFU and histological analysis, there was no difference in morphometric measurements of the injured footpad among experimental groups Figure S3B in Supplementary Material.

NLRP3 inflammasome does not contribute to fungal clearance in a murine chromoblastomycosis model. WT uninfected mice were used as control. These data indicate that F. Studies examining innate immune cell recognition of F. In this study, we demonstrate that the main agent fosnecae CBM, F. One fonscae aspect shown to determine NLRP3 inflammasome activation during fungal infection is morphogenesis.

We show here that live F. This suggests that an invading aggressive hyphal form may be necessary to trigger the inflammatory response Actually, in lung tissues of NLRP3-deficient mice, minimal inflammatory reaction to Aspergillus hyphae infection is observed Another important aspect that influences NLRP3 inflammasome activation during infectious processes is the host cell type.

Indeed, differently from what is shown in macrophages, F. Consistent with this observation, our group previously showed that P. These results are in line with the fact that NLRP3 concentration is critical to the efficacy of inflammasome activation 31and NLRP3 protein levels under steady-state conditions and after PRR engagement are higher in dendritic cells when compared with macrophages 43 Furthermore, in vivo murine splenic conventional dendritic cells reveal constant high Nlrp3 transcript levels Thus, both fungal form and phagocyte type are critical factors that dictate NLRP3 inflammasome activation in fungal infections.

CLRs are the major PRRs family for the recognition of fungal carbohydrate residues and have been associated with the priming step of fonwecae activation in several pedrpsoi infections Dectin-1 and dectin-2 double-deficient dendritic cells infected with Trichophyton rubrum or H.

This is in line with the fact that dectin-1 pedrosoii dectin-2 are required for the development of Th17 cells in mice subcutaneously infected with F. It is noteworthy that dectin-3 can form fonzecae with dectin-2 for sensing and mediation of host protective anti- C. In addition, dectin-3 is necessary for the development of vaccine-induced Th17 cells that are associated with protection against the fungal pathogen Blastomyces dermatitidis The role of dectin-3 fonxecae the recognition of F.

Furthermore, IL-6 production was not significantly altered in dectindeficient cells. In this context, our results suggest that, contrary to conidia, F.

This result parallels those showing Syk and Nfkb1 upregulated transcripts induced by F. Using a fluorescence-based assay, we demonstrated that only F. Caspase-8 can also function in a Fonsecqe inflammasome activation manner, as demonstrated in phagocytes infected with A.