Stimulation, inhibition and death of macrophages infected with Trichophyton rubrum

Campos, M.R.M.; Russo, Marco; Gomes, E. A.; Almeida, Sandro Rogério de

doi:10.1016/j.micinf.2005.07.028

Cited by 72 publications

(71 citation statements)

References 29 publications

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“…Indeed, the M. canis SC consist of a mix of proteins, some of which being potentially able to negatively modulate the immune response. Such immunomodulatory effects have already been revealed for other dermatophytes, such as Trichophyton rubrum able to grow inside macrophages after phagocytosis (Campos et al, 2006). Therefore, the characterisation and the selection of Vaccination induced a strong antibody response towards the SC and the production of IFNγ by PBMCs.…”

Section: Discussionmentioning

confidence: 91%

Assessment of immunogenicity and protective efficacy of Microsporum canis secreted components coupled to monophosphoryl lipid-A adjuvant in a vaccine study using guinea pigs

Cambier

Băguţ

Heinen

et al. 2015

Veterinary Microbiology

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Microsporum canis is the most common dermatophyte in pets and is of zoonotic importance but currently there is no effective vaccine available to prevent dermatophytosis. The aim of this work was to assess the immunogenicity and protective efficacy of secreted components (SC) from M. canis adjuvanted with the monophosphoryl lipid-A (MPLA), in a vaccine study using the guinea pig as an experimental model. Animals were vaccinated with either the SC adjuvanted with the MPLA, the MPLA adjuvant alone or PBS three times at two-week intervals, until 42 days prior to M. canis infection. A blind evaluation of dermatophytosis symptoms development and fungal persistence in skin was monitored weekly. The antibody response towards the SC and the levels of Interferon (IFN)γ and Interleukin-4 expressed in peripheral blood mononuclear cells were assessed along or at the end of the study period respectively. The animals that received MPLA had a significantly lower clinical score than those inoculated with PBS. However, no significant difference was observed between the guinea pigs vaccinated with the SC adjuvanted with the MPLA and those having received MPLA alone. The results also showed that vaccination induced a strong antibody response towards the SC and an increase in IFNγ mRNA level. Our results show that the MPLA adjuvant used in this vaccine study can induce per se a partial protection against a M. canis infection. Although they induce a delayed-type hypersensitivity reaction in guinea pigs, the SC do not confer a protection under the present experimental conditions.

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Section: Discussionmentioning

confidence: 91%

Assessment of immunogenicity and protective efficacy of Microsporum canis secreted components coupled to monophosphoryl lipid-A adjuvant in a vaccine study using guinea pigs

Cambier

Băguţ

Heinen

et al. 2015

Veterinary Microbiology

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“…13 In order to assess the role of inflammasomes in response to T.rubrum, we first analyzed the interaction between T.rubrum conidia and BMDMs (Fig. 1A).…”

Section: Trubrum Conidia Induces Il-1b Production In Bmdmsmentioning

confidence: 99%

“…Associated to this process, we detect production of inflammatory cytokines, e.g., TNF-a, that would feed the inflammation observed in this disease. 13,14 However, up to date, the current role of inflammasomes and IL-1 signaling in response to T.rubrum has not been characterized. In this work, we investigated the role of the NLRP3 inflammasome in macrophages against T.rubrum conidia and how IL-1 signaling influences the outcome of this interaction.…”

Section: Introductionmentioning

confidence: 99%

“…Conidia were obtained as previously described. 13 Briefly, a 14 days-old culture growing in Sabouraud Agar (Difco) at 30 C was transferred to Potato-broth medium (Difco) and kept at 30 C and constant rotation (200 rpm) for 3 days. The suspension was filtered in cell strainer 40 mm (BD) and the suspension was washed 2 times with 0.1% Tween 80 (Synth) in PBS 1£ (Na 2 HPO 4 18 mM; NaH 2 PO 4 .H 2 O 3 mM and NaCl 140 mM in miliQ water, salts from Synth).…”

Section: Introductionmentioning

confidence: 99%

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IL-1 signaling inhibits Trichophyton rubrum conidia development and modulates the IL-17 response in vivo

2015

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Dermatophytosis are one of the most common fungal infections in the world. They compromise keratinized tissues and the main etiological agent is Trichophyton rubrum. Macrophages are key cells in innate immunity and prominent sources of IL-1b, a potent inflammatory cytokine whose main production pathway is by the activation of inflammasomes and caspase-1. However, the role of inflammasomes and IL-1 signaling against T.rubrum has not been reported. In this work, we observed that bone marrow-derived macrophages produce IL-1b in response to T.rubrum conidia in a NLRP3-, ASC-and caspase-1-dependent fashion. Curiously, lack of IL-1 signaling promoted hyphae development, uncovering a protective role for IL-1b in macrophages. In addition, mice lacking IL-1R showed reduced IL-17 production, a key cytokine in the antifungal defense, in response to T.rubrum. Our findings point to a prominent role of IL-1 signaling in the immune response to T.rubrum, opening the venue for the study of this pathway in other fungal infections.

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“…It has been proposed that T. rubrum may have developed evasion mechanisms to escape or even to suppress the host immune responses [9][10][11]. It is well known that patients that resolve this infection do so using cellular immunity (Th1-type) as the main resource controlling the fungus [12].…”

Section: Introductionmentioning

confidence: 99%

Trichophyton rubrum manipulates the innate immune functions of human keratinocytes

et al. 2011

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Evasion or subversion of host immune responses have been shown for a variety of microorganisms, and this might be the case for Trichophyton rubrum, the most common pathogenic fungus causing chronic dermatophytosis in humans. Keratinocytes, the main epidermal cells, have important roles as a first defense against microbial challenges in local immune reactions. Epidermal keratinocytes express several Toll-like receptors and produce host defense peptides, cytokines and chemokines in response to various stimuli. We analyzed the expression of Toll-Like receptor TLR2, TLR4, TLR6, and Human Beta Defensin (HBD)-1, HBD-2, Interleukin IL-1b and IL-8 production, when exposing primary keratinocyte cultures to T. rubrum. We observed changes in size and granularity of keratinocytes stimulated with either whole conidia or conidial homogenates compared to other treatments. Intact conidia decreased keratinocytes’ TLR2 and TLR6 expression without affecting that of TLR4, while conidial homogenates increased the expression of these three receptors. Interestingly, whole conidia decreased HBD-1 and HBD-2 production, whereas conidial homogenate increased it. No changes were observed in IL-1b and IL-8 production after stimulation with conidia or conidial homogenate. CONCLUSIONS. Our results suggest that: 1) Keratinocytes can recognize and respond to cell wall components of T. rubrum; 2) Viable intact conidia inhibit TLR-2 and TLR6 expression and decrease HBD-1 and HBD-2 production; 3) Conidial homogenate from T. rubrum increases the expression of TLR2, TLR4 and TLR6 and induces HBD-1 and HBD-2 production; 4) Therefore, innate immune functions of keratinocytes as the first level of local skin immunity are apparently manipulated by T. rubrum, likely to ensure its establishment, persistence and survival.

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Stimulation, inhibition and death of macrophages infected with Trichophyton rubrum

Cited by 72 publications

References 29 publications

Assessment of immunogenicity and protective efficacy of Microsporum canis secreted components coupled to monophosphoryl lipid-A adjuvant in a vaccine study using guinea pigs

Assessment of immunogenicity and protective efficacy of Microsporum canis secreted components coupled to monophosphoryl lipid-A adjuvant in a vaccine study using guinea pigs

IL-1 signaling inhibits Trichophyton rubrum conidia development and modulates the IL-17 response in vivo

Trichophyton rubrum manipulates the innate immune functions of human keratinocytes

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