Chronic wounds are a common and costly complication of diabetes, where multifactorial defects contribute to dysregulated skin repair, inflammation, tissue damage, and infection. We previously showed that aspects of the diabetic foot ulcer microbiota were correlated with poor healing outcomes, but many microbial species recovered remain uninvestigated with respect to wound healing. Here, we focused on Alcaligenes faecalis, a Gram-negative bacterium that is frequently recovered from chronic wounds but rarely causes infection. Treatment of diabetic wounds with A. faecalis accelerated healing during early stages. We investigated the underlying mechanisms and found that A. faecalis treatment promotes reepithelialization of diabetic keratinocytes, a process that is necessary for healing but deficient in chronic wounds. Overexpression of matrix metalloproteinases in diabetes contributes to failed epithelialization, and we found that A. faecalis treatment balances this overexpression to allow proper healing. This work uncovers a mechanism of bacterial-driven wound repair and provides a foundation for the development of microbiota-based wound interventions.

Respiratory syncytial virus (RSV) causes a severe respiratory condition, bronchiolitis, in infants but not in adults. Bronchiolitis is characterised by neutrophilic infiltration in the airways, but whether neutrophils enhance recovery from infection or contribute to its pathology remains unknown.
We used a novel in-vitro model to compare term umbilical cord blood (infant) (n=17 donors) and adult neutrophils (n=15 donors) during migration across RSV-infected differentiated human nasal airway epithelial cells (AECs) in a basolateral to apical direction.
Greater numbers of infant neutrophils (mean (95% CI)) (336 684 (242 352 to 431 015)) migrated across RSV-infected AECs to the apical compartment (equivalent to the airway lumen) compared with adult neutrophils (56 586 (24 954 to 88 218)) (p<0.0001). Having reached the apical compartment of infected AECs, much greater numbers of infant neutrophils (140 787 (103 117 to 178 456)) became apoptotic compared with adult (5853 (444 to 11 261)) (p=0.002). Infant neutrophils displayed much greater expression of CD11b, CD64, neutrophil elastase (NE) and myeloperoxidase (MPO) than adult neutrophils at baseline and at all points of migration. However, as adult neutrophils migrated, expression of CD11b, CD64, NE and MPO became greater than at baseline.
The high proportion of infant neutrophils migrating across RSV-infected AECs correlates with the neutrophilic infiltrate seen in infants with severe RSV bronchiolitis, with large numbers undergoing apoptosis, which may represent a protective mechanism during infection. Compared with adult neutrophils, infant neutrophils already have high expression of surface markers before contact with AECs or migration, with less capacity to increase further in response to RSV infection or migration.
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.

Over two years into the COVID-19 pandemic, the human immune response to SARS-CoV-2 during the active disease phase has been extensively studied. However, the long-term impact after recovery, which is critical to advance our understanding SARS-CoV-2 and COVID-19-associated long-term complications, remains largely unknown. Herein, we characterized multi-omic single-cell profiles of circulating immune cells in the peripheral blood of 100 patients, including covenlesent COVID-19 and sero-negative controls. The reduced frequencies of both short-lived monocytes and long-lived regulatory T (Treg) cells are significantly associated with the patients recovered from severe COVID-19. Consistently, sc-RNA seq analysis reveals seven heterogeneous clusters of monocytes (M0-M6) and ten Treg clusters (T0-T9) featuring distinct molecular signatures and associated with COVID-19 severity. Asymptomatic patients contain the most abundant clusters of monocyte and Treg expressing high CD74 or IFN-responsive genes. In contrast, the patients recovered from a severe disease have shown two dominant inflammatory monocyte clusters with S100 family genes: S100A8 A9 with high HLA-I whereas S100A4 A6 with high HLA-II genes, a specific non-classical monocyte cluster with distinct IFITM family genes, and a unique TGF-β high Treg Cluster. The outpatients and seronegative controls share most of the monocyte and Treg clusters patterns with high expression of HLA genes. Surprisingly, while presumably short-ived monocytes appear to have sustained alterations over 4 months, the decreased frequencies of long-lived Tregs (high HLA-DRA and S100A6) in the outpatients restore over the tested convalescent time (>= 4 months). Collectively, our study identifies sustained and dynamically altered monocytes and Treg clusters with distinct molecular signatures after recovery, associated with COVID-19 severity.

Neutrophils are critically involved in the immune response. Inflammatory stimuli alter the expression status of their surface molecule toolset, while inflammation-stimulated granulopoiesis might also influence their maturation status. Data on neutrophil status in heart failure with reduced ejection fraction (HFrEF) are scarce. The present study aims to evaluate the role of neutrophil CD11b, CD66b and CD64 expression in HFrEF.
A total of 135 HFrEF patients and 43 controls were recruited. Mean fluorescence intensity of the activation/maturation markers CD11b, CD66b and CD64 was measured on neutrophils by flow cytometry. CD10 (neprilysin) expression was simultaneously determined.
Neutrophil CD64 expression was higher in HFrEF compared with controls, while CD11b/CD66b levels were similar. Neutrophil CD11b and CD66b showed a significant direct correlation to neutrophil CD10 expression (rs = 0.573, p < 0.001 and rs = 0.184, p = 0.033). Neutrophil CD11b and CD66b correlated inversely with heart failure severity reflected by NT-proBNP and NYHA class (NT-proBNP: rs = -0.243, p = 0.005 and rs = -0.250, p = 0.004; NYHA class: p = 0.032 and p = 0.055), whereas no association for CD64 could be found. Outcome analysis did not reveal a significant association between the expression of CD11b, CD66b and CD64 and all-cause mortality (p = ns).
The results underline the potential role of neutrophils in HFrEF disease pathophysiology and risk stratification and should stimulate further research, characterizing subpopulations of neutrophils and searching for key molecules involved in the downward spiral of inflammation and heart failure.