Fungal diseases represent an important paradigm in immunology, as they can result from either a lack of recognition by the immune system or overactivation of the inflammatory response. Research in this field is entering an exciting period of transition from studying the molecular and cellular bases of fungal virulence to determining the cellular and molecular mechanisms that maintain immune homeostasis with fungi. The fine line between these two research areas is central to our understanding of tissue homeostasis and its possible breakdown in fungal infections and diseases. Recent insights into immune responses to fungi suggest that functionally distinct mechanisms have evolved to achieve optimal host-fungus interactions in mammals.

Immunity to Fungal Infections

The incidence of opportunistic yeast infections in humans has been increasing over recent years. These infections are difficult to treat and diagnose, in part due to the large number and broad diversity of species that can underlie the infection. In addition, resistance to one or several antifungal drugs in infecting strains is increasingly being reported, severely limiting therapeutic options and showcasing the need for rapid detection of the infecting agent and its drug susceptibility profile. Current methods for species and resistance identification lack satisfactory sensitivity and specificity, and often require prior culturing of the infecting agent, which delays diagnosis. Recently developed high-throughput technologies such as next generation sequencing or proteomics are opening completely new avenues for more sensitive, accurate and fast diagnosis of yeast pathogens. These approaches are the focus of intensive research, but translation into the clinics requires overcoming important challenges. In this review, we provide an overview of existing and recently emerged approaches that can be used in the identification of yeast pathogens and their drug resistance profiles. Throughout the text we highlight the advantages and disadvantages of each methodology and discuss the most promising developments in their path from bench to bedside.

https://biblio.ugent.be/publication/8640794/file/8640795.pdf

Recent trends in molecular diagnostics of yeast infections : from PCR to NGS

The release of extracellular vesicles (EVs) by fungi is a fundamental cellular process. EVs carry several biomolecules, including pigments, proteins, enzymes, lipids, nucleic acids, and carbohydrates, and are involved in physiological and pathological processes. EVs may play a pivotal role in the establishment of fungal infections, as they can interact with the host immune system to elicit multiple outcomes. It has been observed that, depending on the fungal pathogen, EVs can exacerbate or attenuate fungal infections. The study of the interaction between fungal EVs and the host immune system and understanding of the mechanisms that regulate those interactions might be useful for the development of new adjuvants as well as the improvement of protective immune responses against infectious or noninfectious diseases. In this review, we describe the immunomodulatory properties of EVs produced by pathogenic fungi and discuss their potential as adjuvants for prophylactic or therapeutic strategies.

https://journals.asm.org/doi/pdf/10.1128/mSphere.00747-19

Fungal Extracellular Vesicles as Potential Targets for Immune Interventions.

Introduction 
The agents of paracoccidioidomycosis, historically identified as Paracoccidioides brasiliensis, are in fact different phylogenetic species. This study aims to evaluate associations between Paracoccidioides phylogenetic species and corresponding clinical data.


Methods 
Paracoccidioides strains from INI/Fiocruz patients (1998–2016) were recovered. Socio-demographic, epidemiological, clinical, serological, therapeutic and prognostic data of the patients were collected to evaluate possible associations of these variables with the fungal species identified through partial sequencing of the ADP-ribosylation factor (arf) and the 43-kDa-glycoprotein (gp43) genes.


Results 
Fifty-four fungal strains were recovered from 47 patients, most (72.3%) infected in Rio de Janeiro state, Brazil. Forty-one cases were caused by Paracoccidioides brasiliensis and six by Paracoccidioides americana (former PS2). P. brasiliensis was responsible for severe lymph abdominal forms, whereas patients infected with P. americana presented a high rate of adrenal involvement. However, no statistically significant associations were found for all variables studied. P. americana presented 100% reactivity to immunodiffusion, even when tested against antigens from other species, while negative results were observed in 9 (20%) cases caused by P. brasiliensis, despite being tested against a homologous antigen.


Conclusions 
P. brasiliensis and P. americana are sympatric and share similar clinical features and habitat, where they may compete for similar hosts.

/pdf/clinical-features-and-genetic-background-of-the-sympatric-1igzz7c329.pdf

Clinical features and genetic background of the sympatric species Paracoccidioides brasiliensis and Paracoccidioides americana.

OBJECTIVE\nThe purpose of this study was to evaluate retrospectively the profile of patients with oral paracoccidioidomycosis referred to two Dental Schools in Belo Horizonte (MG, Brazil) between 1955 and 1998. Despite the importance of the oral manifestations of this disease, few papers in the English literature have provided epidemiological data.\n\n\nSUBJECTS AND METHODS\nThe medical records of 62 patients presenting oral paracoccidioidomycosis were reviewed in detail. Patient age, gender, race, occupation, site of lesion and type of clinical manifestation of the disease were tabulated.\n\n\nRESULTS\nThere was a predominance of male patients (97%), with a male:female ratio of 30:1. The mean age was 40 years. Most of the patients were farm workers (53%). Some patients presented multiple oral lesions (19 cases, 30%). The fungal lesions were found principally in the alveolar process and gingiva, but were also seen on the palate, lip and buccal mucosa. All patients had chronic proliferative mulberry-like ulcerated oral lesions and the diagnosis was confirmed histologically. The clinical records did not contain notes about pulmonary involvement by the lesions.\n\n\nCONCLUSION\nThe purpose of this study was to describe the epidemiological profile of a specific population with the diagnosis of oral paracoccidioidomycosis. The major goal is to establish a scientific basis for initiating educational programs for prevention and early diagnosis of oral paracoccidioidomycosis.

Oral paracoccidioidomycosis: retrospective study of 55 brazilian patients

Background This review article summarizes and updates the knowledge on paracoccidioidomycosis. P lutzii and the cryptic species of P. brasiliensis and their geographical distribution in Latin America, explaining the difficulties observed in the serological diagnosis. Objectives Emphasis has been placed on some genetic factors as predisposing condition for paracoccidioidomycosis. Veterinary aspects were focused, showing the wide distribution of infection among animals. The cell-mediated immunity was better characterized, incorporating the recent findings. Methods Serological methods for diagnosis were also compared for their parameters of accuracy, including the analysis of relapse. Results Clinical forms have been better classified in order to include the pictures less frequently observesiod. Conclusion Itraconazole and the trimethoprim-sulfamethoxazole combination was compared regarding efficacy, effectiveness and safety, demonstrating that azole should be the first choice in the treatment of paracoccidioidomycosis.

/pdf/paracoccidioidomycosis-current-perspectives-from-brazil-1cpmkwe104.pdf

Ana Carla Pereira

Papers

Paracoccidioidomycosis: Current Perspectives from Brazil.