The interplay between Aspergillus fumigatus and the host immune response in lung infection has been subject of studies over the last years due to its importance in immunocompromised patients. The multifactorial virulence factors of A. fumigatus are related to the fungus biological characteristics, for example, structure, ability to grow and adapt to high temperatures and stress conditions, besides capability of evading the immune system and causing damage to the host. In this context, the fungus recognition by the host innate immunity occurs when the pathogen disrupts the natural and chemical barriers followed by the activation of acquired immunity. It seems clear that a Th1 response has a protective role, whereas Th2 reactions are often associated with higher fungal burden, and Th17 response is still controversial. Furthermore, a fine regulation of the effector immunity is required to avoid excessive tissue damage associated with fungal clearance, and this role could be attributed to regulatory T cells. Finally, in this work we reviewed the aspects involved in the complex interplay between the host immune response and the pathogen virulence factors, highlighting the immunological issues and the importance of its better understanding to the development of novel therapeutic approaches for invasive lung aspergillosis.

Photodynamic treatment with phenothiazinium photosensitizers kills both ungerminated and germinated microconidia of the pathogenic fungi Fusarium oxysporum, Fusarium moniliforme and Fusarium solani.http://researchonline.ljmu.ac.uk/4233/ Article LJMU has developed LJMU Research Online for users to access the research output of the University more effectively. Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Users may download and/or print one copy of any article(s) in LJMU Research Online to facilitate their private study or for non-commercial research. You may not engage in further distribution of the material or use it for any profit-making activities or any commercial gain.The version presented here may differ from the published version or from the version of the record. Please see the repository URL above for details on accessing the published version and note that access may require a subscription. increased the membrane permeability and APDT with NMBN or S137 increased the lipid peroxidation in microconidia of the three Fusarium species. These findings expand the understanding of photodynamic inactivation of filamentous fungi with phenothiazinium PS.

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Antimicrobial Photodynamic Therapy with Phenothiazinium Photosensitizers in non-vertebrate model Galleria mellonella infected with Fusarium keratoplasticum and Fusarium moniliforme. http://researchonline.ljmu.ac.uk/id/eprint/9910/ Article LJMU has developed LJMU Research Online for users to access the research output of the University more effectively. ABSTRACT Fusarium keratoplasticum and Fusarium moniliforme are filamentous fungi common in the environment and cause mycosis in both animals and plants. Human infections include micetomas, keratitis and onychomycosis, while deeper mycosis occurs in immunocompromised patients. Most of the Fusarium spp. are frequently resistant to treatment with currently used antifungals. The frequent occurrence of antifungal resistance has motivated the study of antimicrobial photodynamic therapy as an alternative treatment for fungal infections. Many studies have investigated the in vitrouse of antimicrobial photodynamic therapy to kill fungi, but rarely in animal models of infection. Thus, here we employed the invertebrate wax moth Galleria mellonella to study the in vivo effects of antimicrobial photodynamic therapy with three different phenothiazinium photosensitizers, methylene blue, new methylene blue N and the pentacyclic S137 against infection with microconidia of Fusarium keratoplasticum and Fusarium moniliforme. The effect of antimicrobial photodynamic therapy using these photosensitizers and light-emitting diodes with an emission peak at 635 nm and an integrated irradiance from 570 to 670 nm of 9.8 mW cm -2 was investigated regarding the toxicity, fungal burden, larval survival and cellular immune response. The results from this model indicate that antimicrobial photodynamic therapy with methylene blue, 2 new methylene blue N and S137 is efficient for the treatment of infection with F. keratoplasticum and F. moniliforme. The efficiency can be attributed to the fungal cell damage caused by antimicrobial photodynamic therapy which facilitates the action of the host immune response.

In vitro susceptibilities of Neoscytalidium spp. sequence types to antifungal agents and antimicrobial photodynamic treatment with phenothiazinium photosensitizers http://researchonline.ljmu.ac.uk/7434/ Article LJMU has developed LJMU Research Online for users to access the research output of the University more effectively. Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Users may download and/or print one copy of any article(s) in LJMU Research Online to facilitate their private study or for non-commercial research. You may not engage in further distribution of the material or use it for any profit-making activities or any commercial gain.The version presented here may differ from the published version or from the version of the record. Please see the repository URL above for details on accessing the published version and note that access may require a subscription.

This study evaluated the salivary concentrations of lactoferrin (Lf) in HIV-seropositive and -seronegative subjects correlating these levels with the incidence of periodontal disease, quantity of Candida spp and systemic condition of the HIV-seropositives (viral load and T lymphocytes CD-4+ count and antiretroviral therapy). Whole saliva samples were obtained from 109 subjects who were divided into four groups according to the extent of their HIV infection and their periodontal condition. The salivary Lf concentrations were determined by a standard enzyme-linked immunosorbent assay and the quantification of Candida spp. was obtained from all subjects. Among the HIV- participants, higher concentrations of Lf were found in individuals with periodontal diseases (p<0.0001). A similar result was found for HIV+ participants (p<0.0001). No correlation was found between the concentration of salivary Lf and the quantification of Candida spp or between the Lf concentration and the systemic condition of the HIV+ subjects. The existence of periodontal diseases can modulate an early inflammatory process in the oral mucosa by increasing the expression of Lf, where Lf can act as an antibacterial peptide in HIV- and HIV+ patients. These results suggest that Lf is a possible marker for periodontal diseases in immunocompetent and immunocompromised subjects.

Summary Background Cryptococcus neoformans/ Cryptococcus gattii species complex is composed of encapsulated yeast species that are causative agents of cryptococcosis. The characterisation of pathogenic Cryptococcus species provides useful data for epidemiological studies as well as the clinical diagnosis and treatment of patients. Objectives This study aimed to characterise the epidemiology, antifungal susceptibility and virulence of 72 clinical strains isolated from cryptococcosis cases between 2012 and 2017 in a tertiary reference hospital in south‐eastern Brazil. Methods Species and molecular types were molecularly assessed by PCR and PCR‐restriction fragment length polymorphism (RFLP) of the URA5 gene. Antifungal susceptibility testing was performed according to the CLSI protocols. The virulence was studied in a Galleria mellonella infection model. Results The most frequently isolated strain was C. neoformans molecular type VNI (61/72; 84.7%), although C. neoformans molecular type VNII (3/72; 4.2%) was also isolated. Additionally, C. deuterogattii molecular type VGII (8/72; 11.1%) was present, but most frequently from non‐HIV‐infected patients. Non‐wild‐type phenotype to the antifungals was observed in 26.4% (19/72) of the C. neoformans and C. deuterogattii clinical isolates, and the latter demonstrated higher MIC to fluconazole and itraconazole than C. neoformans clinical isolates. Finally, the virulence of C. neoformans and C. deuterogattii clinical isolates was diverse in G mellonella larvae and uncorrelated with the virulence factors of melanin and capsule. Conclusions The assessment of the spread of cryptococcal species and molecular types as well as the pattern of corresponding antifungal susceptibility and virulence aids in surveil the emergence of resistant strains, ensuring more accurate management of the cryptococcal infection.

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