Immunological aspects of Candida and Aspergillus systemic fungal infections.

Immunological aspects of Candida and Aspergillus systemic fungal infections. Interdiscip Perspect Infect Dis. 2013;2013:102934 Authors: Mueller-Loebnitz C, Ostermann H, Franzke A, Loeffler J, Uharek L, Topp M, Einsele H Abstract Patients with allogeneic stem cell transplantation (SCT) have a high risk of invasive fungal infections (IFIs) even after neutrophil regeneration. Immunological aspects might play a very important role in the IFI development in these patients. Some data are available supporting the identification of high-risk patients with IFI for example patients receiving stem cells from TLR4 haplotype S4 positive donors. Key defense mechanisms against IFI include the activation of neutrophils, the phagocytosis of germinating conidia by dendritic cells, and the fight of the cells of the innate immunity such as monocytes and natural killer cells against germlings and hyphae. Furthermore, immunosuppressive drugs interact with immune effector cells influencing the specific fungal immune defense and antimycotic drugs might interact with immune response. Based on the current knowledge on immunological mechanism in Aspergillus fumigatus, the first approaches of an immunotherapy using human T cells are in development. This might be an option for the future of aspergillosis patients having a poor prognosis with conventional treatment. PMID: 23401680 [PubMed]
Source: Interdisciplinary Perspectives on Infectious Diseases - Category: Infectious Diseases Tags: Interdiscip Perspect Infect Dis Source Type: research

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Mast cells (MCs) have been considered as the core effector cells of allergic diseases. However, there are evidence suggesting that MCs are involved in the mechanisms of fungal infection. MCs are mostly located in the border between host and environment and thus may have easy contact with the external environmental pathogens. These cells express receptors which can recognize pathogen-associated molecular patterns such as Toll-like receptors (TLR2/4) and C-type Lectins receptors (Dectin-1/2). Currently, more and more data indicate that MCs can be interacted with some fungi (Candida albicans, Aspergillus fumigatus and Sporoth...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion: Endogenous endophthalmitis is a sight threatening condition associated with high mortality particularly when caused by Aspergillus spp. in immunocompromised patients. Contrary to the prior published reports of endogenous endophthalmitis outside India, we found an equal distribution of fungal and bacterial organisms among our cases, with predominance of Aspergillus among fungal isolates and Gram-positive organism among bacteria. Fungal infections, especially with Aspergillus spp., resulted in poor visual and survival outcome.
Source: Indian Journal of Ophthalmology - Category: Opthalmology Authors: Source Type: research
We examined the relationship between the metabolic processes of carbon catabolite repression (CCR), nitrogen catabolite repression (NCR) and virulence in a variety of A. fumigatus clinical isolates. A considerable amount of heterogeneity with respect to the degree of CCR and NCR was observed and a positive correlation between NCR and virulence in a neutropenic mouse model of pulmonary aspergillosis (PA) was found. Isolate Afs35 was selected for further analysis and compared to the reference strain A1163, with both strains presenting the same degree of virulence in a neutropenic mouse model of PA. Afs35 metabolome analysis ...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Conclusion and Perspectives CYP51 plays a crucial role in fungal invasive growth, hyphae formation and virulence, and inhibitors targeting CYP51 have always been an important component of antifungal agents. Further researches on fungal CYP51s might set about from the following aspects: First, while the detailed crystal structures of several susceptible pathogenic fungi CYP51 have been elaborated, those of drug-resistant variants are still in hypothesis. If those structures were elucidated, targeting at common drug-resistant CYP51 protein variants could probably be promising. Second, it deserves more in-depth researches to...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Conclusion: This prospective multicenter study provides information on the current incidence and outcome of IFD in the real life setting. Practice variation between the centers may help to ultimately improve antifungal management in children at highest risk for IFDs. Introduction Available data on the incidence and outcome of invasive fungal diseases (IFD) in children treated for a hematological malignancy or undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are mostly based on single site, retrospective studies or on studies performed prior to the availability of newer compounds such as broad-sp...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Conclusions Because the expression of copper tolerance genes is critical for the survival and virulence of fungal pathogens, pharmacological disruption of the function of copper tolerance genes would be predicted to have the following beneficial effects: (1) Induce fungal death: the loss of copper tolerance genes would lead to toxic levels of copper that would be expected to have fungistatic and/or fungicidal effects on the organism. (2) Enhance the activity of current antifungal drugs: the clinical efficacy of current antifungal drugs may be compromised by intrinsic or acquired resistance. Combination antifungal therapy ...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
In this study they also showed PTX3 localized in NETs formed after neutrophil activation (5). Proteomics analysis revealed that PTX3 forms complexes with two anti-microbial proteins [azurocidin (AZU1) and myeloperoxidase (MPO)] associated to NETs (30). More recently, PTX3 localization in NETs has been confirmed, and the colocalization with AZU1 and MPO has been defined more accurately (31). Further investigation will be needed to understand the involvement of PTX3 interaction with AZU1 and MPO in their antibacterial role during NET formation. Regulation of Complement Activation PTX3 interaction with microorganisms is not...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions: These results demonstrate ISAV to be a safe and effective alternative for antifungal ppx in treatment-naïve pts with AML/MDS undergoing induction therapy with a variety of different regimens. ISAV's weak inhibition of P-glycoprotein and lack of risk of QT prolongation may make ISAV particularly attractive for antifungal ppx in the era of recently approved or emerging AML therapies such as enasidenib, ivosidenib, midostaurin and quizartinib.DisclosuresBose: CTI BioPharma: Research Funding; Constellation Pharmaceuticals: Research Funding; Blueprint Medicines Corporation: Research Funding; Celgene Corporatio...
Source: Blood - Category: Hematology Authors: Tags: 613. Acute Myeloid Leukemia: Clinical Studies: Poster II Source Type: research
Conclusions: These data provide support for a once-weekly rezafungin dosing regimen for prevention of A. fumigatus infections among BMT patients. The effectiveness of current antifungal prophylactic regimens is frequently limited by safety, tolerability, drug interactions, adherence, pill burden and patient factors such as mucositis or background chemotherapeutic regimens. In addition to the excellent safety, tolerability, and lack of drug interactions exhibited by echinocandin agents, the favorable PK profile of rezafungin presents the opportunity to mitigate the typical challenges faced when administering IFI prophylaxis...
Source: Blood - Category: Hematology Authors: Tags: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Poster I Source Type: research
Conclusion: Patterns of invasive fungal infections are changing in many ways. In the midst of these evolving trends, IFI of the respiratory tractcontinue to remain important causes of morbidity and mortality. Diagnostic tools can be adequately used only if the treating physician is aware of the propensity of patients to acquire a fungal infection. Thus, continuous awareness and education is crucial for successful management of patients. Judicious use of antifungal medications as prophylactic measures must be employed, particularly in the critically ill and patients of HIV.
Source: Indian Journal of Medical Microbiology - Category: Microbiology Authors: Source Type: research
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