Fungal spore swelling and germination are restricted by the macrophage phagolysosome.

Many species of medically important fungi are prolific in the formation of asexual spores. Spores undergo a process of active swelling and cell wall remodelling before a germ tube is formed and filamentous growth ensues. Highly elongated germ tubes are known to be difficult to phagocytose and pose particular challenges for immune phagocytes. However, the significance of the earliest stages of spore germination during immune cell interactions has not been investigated and yet this is likely to be important for defence against sporogenous fungal pathogens. We show here that macrophages restrict the early phases of the spore germination process of Aspergillus fumigatus and Mucor circinelloides including the initial phase of spore swelling, spore germination and early polarised growth. Macrophages are therefore adept at retarding germination as well as subsequent vegetative growth which is likely to be critical for immune surveillance and protection against sporulating fungi.

Erratum to "The nature of the fungal cargo induces significantly different temporal programmes of macrophage phagocytosis" [Cell Surf. 8 (2022) 100082].

[This corrects the article DOI: 10.1016/j.tcsw.2022.100082.].

The nature of the fungal cargo induces significantly different temporal programmes of macrophage phagocytosis.

Phagocytosis is an essential component of our immune defence against fungal pathogens. Differences in the dynamics of phagocyte migration, recognition, uptake and phagolysosome maturation are dependent on the characteristics of the fungal cargo, and in particular to differences in cell wall composition and cellular morphology. However, studies that have focused on phagocyte interactions with individual fungal species have not enabled comparisons in the kinetics of these interactions to be made between these different species. We therefore used live cell video microscopy to examine the temporal dynamics of phagocytosis for a range of fungal cargoes by thioglycollate-elicited peritoneal macrophages from C57BL/6 mice. Uniform populations of macrophages were challenged at the same time with yeast cells of Candida albicans, Candida glabrata, Saccharomyces cerevisiae and Cryptococcus neoformans (wild-type and an acapsular mutant, cap59Δ), and spores of Aspergillus fumigatus and Mucor circinelloides to enable standardized comparative interactions to be quantified from different stages of phagocytosis. Differences in the rate of uptake of fungal cells varied by up to 26-fold, whilst differences in time to induce phagosome acidification varied by as much as 29-fold. Heat-killing or opsonizing the fungal targets markedly affected the kinetics of the interaction in a species-specific manner. Fungal and macrophage killing assays further revealed cargo-specific differences in phagocytosis and diversity in fungal evasion mechanisms. Therefore, simultaneous assessment of the interaction of macrophages with different fungal pathogens highlighted major differences in the kinetics and growth responses during fungus-phagocyte interactions that are likely to impact on pathogenesis and virulence.

Neural Correlates Associated With Suicide and Nonsuicidal Self-injury in Youth.

There is no definitive neural marker of suicidal thoughts and behaviors (STBs) or nonsuicidal self-injury (NSSI), and relative to adults, research in youth is more limited. This comprehensive review focuses on magnetic resonance imaging studies reporting structural and functional neural correlates of STBs and NSSI in youth to 1) elucidate shared and independent neural alternations, 2) clarify how developmental processes may interact with neural alterations to confer risk, and 3) provide recommendations based on convergence across studies. Forty-seven articles were reviewed (STBs = 27; NSSI = 20), and notably, 63% of STB articles and 45% of NSSI articles were published in the previous 3 years. Structural magnetic resonance imaging research suggests reduced volume in the ventral prefrontal and orbitofrontal cortices among youth reporting STBs, and there is reduced anterior cingulate cortex volume related to STBs and NSSI. With regard to functional alterations, blunted striatal activation may characterize STB and NSSI youth, and there is reduced frontolimbic task-based connectivity in suicide ideators and attempters. Resting-state functional connectivity findings highlight reduced positive connectivity between the default mode network and salience network in attempters and show that self-injurers exhibit frontolimbic alterations. Together, suicidal and nonsuicidal behaviors are related to top-down and bottom-up neural alterations, which may compromise approach, avoidance, and regulatory systems. Future longitudinal research with larger and well-characterized samples, especially those integrating ambulatory stress assessments, will be well positioned to identify novel targets that may improve early identification and treatment for youth with STBs and NSSI.