Innate and Adaptive Immune Responses Induced by Aspergillus fumigatus Conidia and Hyphae.

Previous research indicated that hyphae of Aspergillus fumigatus (A. fumigatus) rather than conidia could successfully build a pulmonary aspergillosis model in immunocompetent mice. In this study, we compared the immune responses induced by hyphae and conidia to explore the possible mechanism of this striking phenomenon. Herein, a novel method was designed and adopted to quantify hyphal fragments. Murine macrophages RAW264.7 and human peripheral blood mononuclear cells were stimulated by A. fumigatus hyphae and conidia in vitro, respectively, and then immunological reactions were measured. Male C57BL/6 mice were challenged with conidia and hyphae through intratracheal inoculation. Dynamic conditions of mice were recorded, and RNA-seq measured corresponding immune responses. The results of the study confirmed that hyphae could induce more intensive inflammation than conidia in vitro and in vivo. However, macrophages revealed a higher production of ROS and M1 polarisation in response to conidia stimuli. Additionally, conidia could promote Th1 cell differentiation, while hyphae could increase the CD4/CD8 ratio. RNA-seq validated the fact that those multiple immunologically relevant pathways were more strongly activated by hyphae than conidia, which also promoted Th2 cell differentiation and suppressed Th1 signalling. Both hyphae and conidia could activate Th17 signalling. In general, conidia and hyphae induced distinctly different host immune responses, and the immune responses induced by conidia played a better protective effect. Therefore, the unique function of hyphae in the spread and infection of Aspergillus should be emphasised, and more research is required to clarify the underlying mechanisms for better understanding and management of aspergillosis.

The dynamic changes of psychosomatic symptoms in three waves of COVID-19 outbreak and fatigue caused by enduring pandemic in China.

BACKGROUND: Two years have passed since the 2019 novel coronavirus disease (COVID-19) was first reported. The persistent pandemic might lead to severe psychosomatic problems and fatigue. In addition, the recent rapid rising COVID-19 cases in China have become a trending issue. Therefore, this study aimed to investigate the dynamic changes in psychosomatic problems at the initial and current stages of the pandemic. METHODS: Three waves of cross-sectional online survey were conducted during the initial COVID outbreak in China. The psychosomatic symptom scale (PSSS), perceived stress scale (PSS), and pandemic fatigue scale (PFS) were used to assess the psychosomatic problems, stress, and fatigue. RESULTS: 4317, 1096, and 2172 participants completed the first, second, and third surveys. The prevalence of psychosomatic disorder was 22 %, 28 %, and 39 %, respectively. The network structure of PSSS symptoms has not significantly changed as the pandemic progresses. However, the global strength of the PSSS networks, indicating the overall connectivity, in the third wave was significantly higher than in the first wave (s = 0.54, P = 0.007). The most central symptoms in the first and third wave networks were depressed mood and tiredness. The PFS score was higher in the people concerned with indirect impact than those concerned with health (P < 0.001). PFS has positive relationships with PSSS and PSS score (R = 0.41, P < 0.001 and R = 0.35, P < 0.001, respectively). CONCLUSIONS: The persistence of the pandemic caused critical psychosomatic issues, stress, and indirect burden over time, leading to inevitable fatigue. People endured needing immediate attention to prevent or reduce psychosomatic disorders.

Adult-Onset Familial Hemophagocytic Lymphohistiocytosis Presenting with Annular Erythema following COVID-19 Vaccination.

Familial hemophagocytic lymphohistiocytosis (HLH) is a rare genetic and life-threatening immunodeficiency disease. Here, we present a 38-year-old male who initially developed multiple annular to irregular erythema accompanied by a fever after COVID-19 vaccination. He was diagnosed with HLH with evidence of leukocytopenia in a full blood test, elevations of ferritin and sCD25, decreased NK cell function, and hemophagocytosis of a bone marrow biopsy specimen. A genetic examination revealed two probable disease-causing heterozygous mutations on UNC13D associated with type 3 familial HLH. A review of the case reports relevant to HLH following COVID-19 vaccination and the cutaneous manifestations of HLH with genetic defects suggests the necessity that individuals with preexisting immune dysregulation or diseases not classified should be cautious about COVID-19 vaccination and reminds clinicians that various recalcitrant skin lesions may be a sign of HLH.

Amplification of Olfactory Signals by Anoctamin 9 is Essential for Mammalian Olfaction: a Risk Factor for the Covid-19-associated Anosmia (preprint)

Sensing smells of foods, prey, or predators determines animal survival. Olfactory sensory neurons in the olfactory epithelium (OE) detect odorants, where cAMP and Ca2+ play a significant role in transducing odorant inputs to electrical activity. Here we show Anoctamin 9, a cation channel activated by cAMP/PKA pathway, is expressed in the OE and amplifies olfactory signals. Ano9-deficient mice had reduced olfactory behavioral sensitivity, electro-olfactogram signals, and neural activity in the olfactory bulb. In line with the difference in olfaction between birds and other vertebrates, chick ANO9 failed to respond to odorants, whereas chick CNGA2, a major transduction channel, showed greater responses to cAMP. Importantly, single-cell transcriptome data from Covid-19 patients revealed that Ano9 transcripts were markedly suppressed among genes in the olfactory signal pathway. The signal amplification by ANO9 is essential for mammalian olfactory transduction, whose downregulation may be a risk factor for the olfactory dysfunction in Covid-19 patients.