Oral mucosal colonization by (Ca) is benign in healthy people but progresses to deeper infection known as oropharyngeal candidiasis (OPC) that may become disseminated when combined with immunosuppression. Cortisone-induced immunosuppression is a well-known risk factor for OPC, however the mechanism by which it permits infection is poorly understood. Neutrophils are the primary early sentinels preventing invasive fungal growth, and here we identify that neutrophil functional complexes known as swarms are crucial for preventing Ca invasion which are disrupted by cortisone. Neutrophil swarm function required leukotriene B4 receptor 1 (BLT1) expression, and swarms were further characterized by peripheral association of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) showing that OPC recruits PMN-MDSCs to this site of infection. Furthermore, PMN-MDSCs associated with Ca hyphae had no direct antifungal effect but showed prolonged survival times and increased autophagy. Thus neutrophil swarms are complex structures with spatially associated PMN-MDSCs that likely contribute immunoregulatory functions to resolve OPC. These swarm structures have an important function in preventing deep invasion by Ca within the oral mucosa and represent a mechanism for increased disease severity under immune deficient clinical settings.
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http://dx.doi.org/10.21203/rs.3.rs-3346012/v1 | DOI Listing |
Microbiol Spectr
November 2024
BioMEMS Resource Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Unlabelled: Neutrophils communicate with one another and amplify their destructive power through swarming, a collective process that synchronizes the activities of multiple neutrophils against one target. The sequence of activities contributing to swarming against clusters of fungi has been recently uncovered. However, the molecular signals controlling the neutrophils' activities during the swarming process are just emerging.
View Article and Find Full Text PDFJ Leukoc Biol
November 2024
Department of Oral Biology, University at Buffalo, Buffalo, NY, USA.
Oral mucosal colonization by C. albicans (Ca) is benign in healthy people but progresses to deeper infection known as oropharyngeal candidiasis (OPC) that may become disseminated when combined with immunosuppression. Cortisone use and neutropenia are risk factors for invasive mucosal fungal infections, however the mechanisms are poorly understood.
View Article and Find Full Text PDFJHEP Rep
November 2024
European Foundation for the Study of Chronic Liver Failure (EF CLIF), European Association for the Study of the Liver (EASL)-CLIF Consortium, and Grifols Chair, Barcelona, Spain.
Background & Aims: Patients with acutely decompensated (AD) cirrhosis are immunocompromised and particularly susceptible to infections. This study investigated the immunomodulatory actions of albumin by which this protein may lower the incidence of infections.
Methods: Blood immunophenotyping was performed in 11 patients with AD cirrhosis and 10 healthy volunteers (HV).
Nat Commun
October 2024
Department of Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Listeria monocytogenes (LM) possesses the ability to breach multiple barriers and elicit intricate immune responses. However, there remains a lack of explicit understanding regarding how LM evades innate immune surveillance within the body. Here, we utilized liver intravital imaging to elucidate the dynamic process of LM during infection in the liver.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2024
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.
While the acute inflammatory response to harmful stimuli is protective, unrestrained neutrophil swarming drives collateral tissue damage and inflammation. Biosynthesized from omega-3 essential polyunsaturated fatty acids, resolvins are a family of signaling molecules produced by immune cells within the resolution phase to orchestrate return to homeostasis. Understanding the mechanisms that govern biosynthesis of these potent molecules gives insight into stimulating endogenous resolution and offers fresh opportunities for preventing and treating excessive inflammation.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!