Figure - available from: Frontiers in Cellular and Infection Microbiology
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The dynamics of fungal infection in Tm-infected TLR2+/+ and TLR2−/− mice. (A) Recovery of viable fungi from footpads of Tm-infected mice 24 h and 7 days p.i. Results are expressed as mean ± SD (Unpaired t-test: ***P < 0.001). (B) Footpad of a naïve mouse (HE). (C) Footpad of a TLR2+/+ mouse 24 h after inoculation, showing a typical acute inflammatory response, characterized by an influx of neutrophils, edema, and abscess formation (HE). (D) Footpad of a TLR2+/+ mouse 7 days after infection, showing an initial granulomatous reaction with a small number of neutrophils and modified macrophages; details are shown in (E) (HE). (F) Footpad of a TLR2−/− mouse 7 days after infection, showing a well-organized granulomatous response, characterized by modified macrophages and epithelioid cells (arrow) (HE).
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Dermatophytosis is one of the most common human infections affecting both immunocompetent individuals and immunocompromised patients, in whom the disease is more aggressive and can reach deep tissues. Over the last decades, cases of deep dermatophytosis have increased and the dermatophyte-host interplay remains poorly investigated. Pattern recognit...
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Aim
The present study aimed to investigate the effect of intravenous immunoglobulin (IVIG) on regulatory T (Treg) cells derived from immunosuppressed mice with Pseudomonas aeruginosa (PA) pneumonia.
Methods
A total of 108 BALB/c mice were randomly divided into the following groups: control group (Control), immunosuppressed group (IS), PA pneumonia...
Dermatophytes include fungal species that infect humans, as well as those which also infect other animals or only grow in the environment. The dermatophyte species Trichophyton rubrum is a frequent cause of skin infection in immunocompetent individuals. While members of the T. rubrum species complex have been further categorized based on various mo...
Citations
... TLR2 blockade by neutralizing antibodies disrupts monocyte fungicidal activity against T. rubrum and monocyte TNF-a secretion, suggesting the importance of and requirement for TLR2 for effective conidium phagocytosis, and the absence of TLR2 in human monocytes may disrupt the successful inflammatory response (133). However, another study showed that TLR2-deficient and wild-type (WT) mice exhibited similar control of deep dermatophyte infection; nevertheless, the TLR2-deficient mice exhibited a notable elevation in IFN-g, IL-10, and IL-17 production and an increased percentage of splenic regulatory T (Treg) cells (134). Therefore, how TLR2 exerts its immune activities during dermatophyte infection is still not completely clear, and more investigations are needed to elucidate its role in protection against dermatophytosis. ...
Dermatophytosis is a common superficial infection caused by dermatophytes, a group of pathogenic keratinophilic fungi. Apart from invasion against skin barrier, host immune responses to dermatophytes could also lead to pathologic inflammation and tissue damage to some extent. Therefore, it is of great help to understand the pathogenesis of dermatophytes, including fungal virulence factors and anti-pathogen immune responses. This review aims to summarize the recent advances in host-fungal interactions, focusing on the mechanisms of anti-fungal immunity and the relationship between immune deficiency and chronic dermatophytosis, in order to facilitate novel diagnostic and therapeutic approaches to improve the outcomes of these patients.
... - [78] T. interdigitale 1. Enhance M1-type activation to further improve its antifungal ability by using extracellular vesicles through TLR2. ...
... Moreover, Dectin-1 has been confirmed to be a key pattern recognition receptor involved in the immunology of dermatophytes. Mutations in CARD9 are usually associated with the occurrence of deep dermatophytes in non-immunosuppressed patients [31,78]. An analysis of different fungal infections in Turkey found that the production of IL-17 and IL-22 from circulating T cells in patients with autosomal recessive CARD9 mutations was decreased. ...
... In addition, the expression of Tlr2 in macrophages was increased when diabetic mice were infected with Trichophyton mentagrophytes in the deep layer of the skin. The infection is often accompanied by excessive inflammatory reactions caused by dense pleomorphic inflammatory infiltration, severe injury in the necrotic area, and a lower fungal scavenging effect caused by decreased hydrogen peroxide production [78]. The reason for this is the activation of multiple inflammatory pathways caused by excessive polarization of M1 macrophages in diabetic patients. ...
Macrophages, the first line of defense against invasive fungi in the innate immune system, are widely distributed in the blood and tissues of the body. In response to various internal and external stimulators, macrophages can polarize into classically activated macrophages (M1) and alternatively activated macrophages (M2). These two types of polarized macrophages play different roles in antifungal activity and in maintaining the steady-state balance between inflammation and tissue repair. However, the antifungal mechanisms of M1- and M2-type macrophages have not been fully described. In this review, the immune regulatory mechanisms against pathogenic fungi of these two classical types of macrophages in various tissues are summarized. The effects of antifungal factors on macrophage differentiation are also highlighted. The description of these data, on the one hand provides valuable insight for future investigations and also highlights new strategies for the treatment of pathogenic fungal infections.
... Hyperglycemic mice have previously been used to investigate the host response to dermatophytosis (Venturini et al., 2011;Fraga-Silva et al., 2015;Almeida et al., 2017). Clinical picture of dermatophytosis by T. mentagrophytes on the skin of mice and efficacy of antifungal drugs: Skin of the back of diabetic mice were infected with 1 × 10 7 conidia and the clinical picture of infection was monitored over time. ...
Dermatophytosis is one of the most prevalent fungal infections and a major public health problem worldwide. Recent years have seen a change in the epidemiological patterns of infecting fungi, corresponding to an alarming rise in the prevalence of drug-recalcitrant dermatophyte infections. In patients with diabetes mellitus, dermatophytosis is more severe and recurrent. The potency of promising new antifungal drugs in the pipeline must be expanded to include dermatophytosis. To facilitate this effort, we established a clinically pertinent mouse model of dermatophyte infections, in which diabetic mice were infected with Trichophyton mentagrophytes on abraded skin. The diabetic mouse model was optimized as a simple and robust system for simulating dermatophytoses in diabetic patients. The outcome of infection was measured using clinical and mycological parameters. Infected mice with fungal lesions were treated with oral and topical formulations of terbinafine or topical administration of the FDA-approved and repurposed pan-antifungal drug alexidine dihydrochloride (AXD). In this model, AXD was found to be highly effective, with outcomes comparable to those of the standard of care drug terbinafine.
... On the other hand, published data using a deep dermatophytosis model in TLR-2 deficient mice subcutaneously infected with T. mentagrophytes demonstrated that fungal interaction with TLR-2 suppresses the inflammatory response of peritoneal macrophages and the production of IL-17, IL-10 and IFN-g (interferon-gamma) by splenocytes (56). Coincidentally, we observed a lower fungal burden in the skin of TLR-2 deficient mice compared to WT using an epicutaneous model of M. canis infection (Beccacece I., unpublished data). ...
Dermatophytoses (ringworms) are among the most frequent skin infections and are a highly prevalent cause of human disease worldwide. Despite the incidence of these superficial mycoses in healthy people and the compelling evidence on chronic and deep infections in immunocompromised individuals, the mechanisms controlling dermatophyte invasion in the skin are scarcely known. In the last years, the association between certain primary immunodeficiencies and the susceptibility to severe dermatophytosis as well as the evidence provided by novel experimental models mimicking human disease have significantly contributed to deciphering the basic immunological mechanisms against dermatophytes. In this review, we outline the current knowledge on fungal virulence factors involved in the pathogenesis of dermatophytoses and recent evidence from human infections and experimental models that shed light on the cells and molecules involved in the antifungal cutaneous immune response. The latest highlights emphasize the contribution of C-type lectin receptors signaling and the cellular immune response mediated by IL-17 and IFN-γ in the anti-dermatophytic defense and skin inflammation control.
... Owing to the amphiphilic nature, SL-YS3 might alter the permeability of the cell membrane of T. mentagrophytes, interfering with the ion transport leading to cell membrane rupture and cell death. evaluation of the activities of several antifungal agents (Hay et al., 1983;Almeida et al., 2017). The culture of the tissue samples yielded a negative result in SL-YS3, and TRB treated groups, which could be considered clinically cured in the therapeutic process. ...
Trichophyton mentagrophytes, a zoophilic species, is one of the most frequently isolated dermatophytes in many parts of the world. This study investigated the efficacy of a sophorolipid (SL-YS3) produced by Rhodotorula babjevae YS3 against dermatophytosis caused by Trichophyton mentagrophytes. SL-YS3 was characterized by gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography coupled with electrospray mass spectrometry (UPLC-ESI-MS). SL-YS3 comprised of six different fatty acids as the hydrophobic components of constituent congeners and sophorose as the hydrophilic component. Inhibitory effects of purified SL-YS3 against hyphal growth was found to be 85% at 2 mg ml-1 concentration, and MIC was 1 mg ml-1. Microscopic examination with scanning electron microscopy (SEM), atomic force microscopy (AFM), and confocal laser scanning microscopy (CLSM) revealed that SL-YS3 exerts its effect by disrupting cell membrane integrity causing cell death. SL-YS3 was also effective in reducing the biofilms formed by T. mentagrophytes, which was observed spectrophotometrically with crystal-violet staining and further validated with SEM and CLSM studies of treated biofilms. In vivo studies in a mouse model of cutaneous dermatophytosis involving macroscopic observations, percent culture recovery from skin samples, and histopathological studies showed that SL-YS3 could effectively cure the infected mice after 21 days of topical treatment. Terbinafine (TRB) was used as a standard drug in the experiments. We demonstrate, for the first time, the antidermatophytic activity of a sophorolipid biosurfactant. The findings are suggestive that SL-YS3 can be formulated as a novel antifungal compound to treat cutaneous mycoses caused by T. mentagrophytes.
... TLR2 can be activated by glycosylphosphatidylinositols (GPIs) presented on some protozoa and participates in the host defense against parasite infection (10), such as Toxoplasma gondii and Trypanosoma cruzi (17,18). However, TLR2 has also been suggested to diminish the development of adaptive immune responses during experimental deep dermatophytosis and to act to intensify a non-protective inflammatory response (19). For Giardia, it has been shown that Giardia trophozoites lysate may interfere with the activation of dendritic cell (DC) through TLR2 in vitro (20). ...
... TLR2 also participates in the host defense against parasite infection such as T. gondii and T. cruzi (10,17,18). However, TLR2 −/− mice display increased clearance of Dermatophyte Trichophyton mentagrophytes in the setting of hyperglycemia (19). In this study, we found that Giardia infection led to a decreased parasite burden, short parasite persistence and an increased weight gain rate in infected TLR2 −/− mice compared with in infected WT mice. ...
Giardia infection is one of the most common causes of waterborne diarrheal disease in a wide array of mammalian hosts, including humans globally. Although numerous studies have indicated that adaptive immune responses are important for Giardia defense, however, whether the host innate immune system such as TLRs recognizes Giardia remains poorly understood. TLR2 plays a crucial role in pathogen recognition, innate immunity activation, and the eventual pathogen elimination. In this study, we investigated the role of TLR2 as a non-protective inflammatory response on controlling the severity of giardiasis. RT-PCR analysis suggested that TLR2 expression was increased in vitro. We demonstrated that Giardia lamblia-induced cytokines expression by the activation of p38 and ERK pathways via TLR2. Interestingly, the expression of IL-12 p40, TNF-α, and IL-6, but not IFN-γ, was enhanced in TLR2-blocked and TLR2−/− mouse macrophages exposed to G. lamblia trophozoites compared with wild-type (WT) mouse macrophages. Further analysis demonstrated that G. lamblia trophozoites reduced cytokines secretion by activating AKT pathway in WT mouse macrophages. Immunohistochemical staining in G. lamblia cysts infected TLR2−/− and WT mice showed that TLR2 was highly expressed in duodenum in infected WT mice. Also, infected TLR2−/− and AKT-blocked mice showed an increased production of IL-12 p40 and IFN-γ compared with infected WT mice at the early stage during infection. Interestingly, infected TLR2−/− and AKT-blocked mice displayed a decreased parasite burden, an increased weight gain rate, and short parasite persistence. Histological morphometry showed shortened villus length, hyperplastic crypt and decreased ratio of villus height/crypt depth in infected WT mice compared with in infected TLR2−/− and AKT-blocked mice. Together, our results suggested that TLR2 deficiency leads to alleviation of giardiasis and reduction of parasite burden through the promotion of proinflammatory cytokines production. For the first time, our results demonstrated that TLR2 played a negative role in host defense against Giardia.
The incidence of skin fungal infections is increasing at an alarming rate worldwide, presenting a major challenge to health professionals. Cutaneous and subcutaneous fungal infections are caused by pathogenic or opportunistic organisms varying from mold, yeasts, to dimorphic fungi. Recently, skin fungal have been increasingly reported and studied, giving rise to crucial breakthroughs in etiology and pathogenesis. This review aims to summarize recent insights into the clinical and etiological characteristics of common skin fungal infections according to different fungal species, as well as remarkable advances in the immune mechanisms. We hope it will be helpful to understand these diverse skin fungal infections, and bring about the latest developments that may facilitate novel diagnostic and therapeutic approaches to improve the outcomes in these patients.
