Sensing the threat posed by Aspergillus infection.
Sensing the threat posed by Aspergillus infection. Curr Opin Microbiol. 2020 Sep 05;58:47-55 Authors: Obar JJ Abstract The mammalian immune system can tune its inflammatory response to the threat level posed by an invading pathogen. It is well established that the host utilizes numerous 'patterns of pathogenicity', such as microbial growth, invasion, and viability, to achieve this tuning during bacterial infections. This review discusses how this notion fits during fungal infection, particularly regarding Aspergillus fumigatus infection. Moreover, how the environmental niches filled by A. fumigatus may drive the evolution of the fungal traits responsible for inducing the strain-specific inflammatory responses that have been experimentally observed will be discussed. Moving forward understanding the mechanisms of the fungal strain-specific inflammatory response due to the initial interactions with the host innate immune system will be essential for enhancing our therapeutic options for the treatment of invasive fungal infections. PMID: 32898768 [PubMed - as supplied by publisher]
Invasive fungal infections caused by Aspergillus (A.) and Mucorales species still represent life-threatening diseases in immunocompromised individuals, and deeper knowledge about fungal interactions with elements of innate immunity, such as complement and platelets, appears essential for optimized therapy. Previous studies showed that galactosaminogalactan secreted by A. fumigatus and A. flavus is deposited on platelets, thereby inducing their activation. Since the altered platelet surface is a putative trigger for complement activation, we aimed to study the interplay of platelets with complement in the presence of fungal...
PMID: 32687390 [PubMed - as supplied by publisher]
PMID: 32687389 [PubMed - as supplied by publisher]
In conclusion, this study demonstrated that validamycin A inhibited the growth of A. flavus and delayed conidial germination. Furthermore, the combined effect of validamycin A with amphotericin B increased A. flavus killing, without significant cytotoxicity to human bronchial epithelial cells. We propose that validamycin A could potentially be used in vivo as an alternative treatment for A. flavus infections. PMID: 32676114 [PubMed]
The role of antifungal prophylaxis in acute myeloid leukemia (AML) continues to be controversial, with national guidelines recommending prophylaxis based on incidence of invasive fungal infection (IFI) to each region. We performed a retrospective, interrupted time series study based on periods where fluconazole was used or not used as prophylaxis during induction for AML. There was a decrease in IFI with fluconazole; however, this was largely driven by probable Aspergillus infection seen in our non-prophylaxis cohort. Our results suggest further investigation of azoles is warranted with consideration of including risk adap...
ConclusionsBronchoscopy could be a reliable procedure for TBA diagnosis in critically ill non ‐neutropenic patients. Whitish plaques ± ulcers were the prominent bronchoscopic changes with reasonable diagnostic accuracy for prediction of TBA.
Conclusions. The emergence of azole-resistant A. fumigatus infections in STAT3-deficiency dramatically impacts both curative and prophylactic antifungal strategies. Physicians following patients with primary immune-deficiencies should be aware of this emerging problem as it complicates management of the patient. PMID: 32459615 [PubMed - as supplied by publisher]
Abstract Fungi are an important but frequently overlooked cause of morbidity and mortality in humans. Life-threatening fungal infections mainly occur in immunocompromised patients, and are typically caused by environmental opportunists that take advantage of a weakened immune system. The filamentous fungus Aspergillus fumigatus is the most important and well-documented mold pathogen of humans, causing a number of complex respiratory diseases, including invasive pulmonary aspergillosis, an often fatal disease in patients with acute leukemia or in immunosuppressed bone marrow or solid organ transplant recipients. Ho...
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.
Conclusion: The blockade of PD-1 on postsepsis aspergillosis presumably reinvigorated exhausted antigen-presenting cells and T cells by upregulating CD86 expression and IFN-γ production, and dampened IL-10 production, which consequently leaded to the attenuation of secondary aspergillosis. The adjunctive anti-PD-1 therapy may become a promising strategy for the advanced immunotherapy against lethal fungal infection.