Immune cells fold and damage fungal hyphae.

Innate immunity provides essential protection against life-threatening fungal infections. However, the outcomes of individual skirmishes between immune cells and fungal pathogens are not a foregone conclusion because some pathogens have evolved mechanisms to evade phagocytic recognition, engulfment, and killing. For example, Candida albicans can escape phagocytosis by activating cellular morphogenesis to form lengthy hyphae that are challenging to engulf. Through live imaging of C. albicans-macrophage interactions, we discovered that macrophages can counteract this by folding fungal hyphae. The folding of fungal hyphae is promoted by Dectin-1, ß2-integrin, VASP, actin-myosin polymerization, and cell motility. Folding facilitates the complete engulfment of long hyphae in some cases and it inhibits hyphal growth, presumably tipping the balance toward successful fungal clearance.

Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis.

Invasive aspergillosis mainly occurs in immunocompromised patients and is commonly caused by Aspergillus fumigatus, while A.nidulans is rarely the causative agent. However, in chronic granulomatous disease (CGD) patients, A. nidulans is a frequent cause of invasive aspergillosis and is associated with higher mortality. Immune recognition of A. nidulans was compared to A. fumigatus to offer an insight into why A. nidulans infections are prevalent in CGD. Live cell imaging with J774A.1 macrophage-like cells and LC3-GFP-mCherry bone marrow-derived macrophages (BMDMs) revealed that phagocytosis of A. nidulans was slower compared to A. fumigatus. This difference could be attributed to slower migration of J774A.1 cells and a lower percentage of migrating BMDMs. In addition, delayed phagosome acidification and LC3-associated phagocytosis was observed with A. nidulans. Cytokine and oxidative burst measurements in human peripheral blood mononuclear cells revealed a lower oxidative burst upon challenge with A. nidulans. In contrast, A. nidulans induced significantly higher concentrations of cytokines. Collectively, our data demonstrate that A. nidulans is phagocytosed and processed at a slower rate compared to A. fumigatus, resulting in reduced fungal killing and increased germination of conidia. This slower rate of A. nidulans clearance may be permissive for overgrowth within certain immune settings.

Bilateral endogenous endophthalmitis due to pseudomonas aeruginosa in a neonate.

BACKGROUND: Bacterial eye infections are rare in the neonatal population and usually come from exogenous spread. Eye infection due to Pseudomonas aeruginosa, although uncommon, may be a devastating disease, especially in premature infants. METHODS: Retrospective review of the clinical chart of a 10-day-old newborn baby with bilateral endogenous Pseudomonas aeruginosa endophthalmitis. RESULTS: The patient presented with leukokoria in both eyes 7 days after the onset of severe septicemia due to endophthalmitis in both eyes. The baby received systemic treatment with meropenem and vancomycin, which the cultured bacteria were susceptible to, but the infection progressed. Intravitreal ceftazidime treatment and later vitrectomy could not prevent complete retina detachment and the progressive evolution to phthisis. CONCLUSION: Aggressive therapy including systemic antibiotics, intravitreous antibiotic injection, and vitrectomy could not prevent a poor outcome leading to retinal detachment and blindness in both eyes. A discussion of the treatment options and a review of the literature are also included.