Biology subjects

Mendes, D. A. G. B.

Publications and source records attributed to Mendes, D. A. G. B..

2 recordsLinked to original sources

bioRxiv2025

A Specialized CD107a+ Macrophage Subset Drives Selective Mycobacterial Phagocytosis

Macrophages are essential for pathogen clearance, yet phagocytic specialization among subsets is poorly defined. Bone marrow-derived macrophages cultured with L929 supernatant or M-CSF separate into FSCloSSCloF4/80loCD11blo (FSCloSSClo) and FSChiSSChiF4/80hiCD11bhi (FSChiSSChi) subsets. Transcriptomic and functional analyses reveal that FSCloSSClo cells possess a hyperphagocytic program driven by enhanced actin cytoskeleton regulators (e.g., Arp2/3) and pro-inflammatory signaling (NF-{kappa}B). These cells excel at internalizing Mycobacterium tuberculosis virulent H37Rv and BCG through actin-mediated, cytochalasin D-sensitive mechanisms. High surface CD107a (LAMP1) expression marks this hyperphagocytic subset and correlates strongly with mycobacterial uptake. FSCloSSClo macrophages produce more TNF and IL-6 upon mycobacterial or TLR2/TLR5 stimulation yet retain IFN-{gamma}-mediated killing capacity. In vivo, CD107a alveolar macrophages in BCG-infected lungs preferentially capture bacilli and upregulate CD195, recapitulating the in vitro phenotype. These findings establish CD107a as a key surface marker of a hyperphagocytic macrophage subset and highlight its role in selective mycobacterial phagocytosis, providing new mechanistic understanding relevant to tuberculosis host defense and therapeutic development. HighlightsO_LIBone marrow-derived FSCloSSCloF4/80loCD11blo macrophage subset excels at M. tuberculosis and BCG uptake C_LIO_LIHyperphagocytic macrophages mount rapid pro-inflammatory TNF/IL-6 responses C_LIO_LICD107a (LAMP1) identifies a pre-existing hyperphagocytic macrophage subset in vitro and in vivo C_LIO_LIBCG infection triggers CD195 (CCR5) upregulation selectively on CD107a alveolar macrophages C_LI

immunology↗

bioRxiv2020

Neuraminidase inhibitors rewire neutrophil function in murine sepsis and COVID-19 patient cells

Neutrophil overstimulation plays a crucial role in tissue damage during severe infections. Neuraminidase (NEU)-mediated cleavage of surface sialic acid has been demonstrated to regulate leukocyte responses. Here, we report that antiviral NEU inhibitors constrain host NEU activity, surface sialic acid release, ROS production, and NETs released by microbial-activated human neutrophils. In vivo, treatment with Oseltamivir results in infection control and host survival in peritonitis and pneumonia models of sepsis. Single-cell RNA sequencing re-analysis of publicly data sets of respiratory tract samples from critical COVID-19 patients revealed an overexpression of NEU1 in infiltrated neutrophils. Moreover, Oseltamivir or Zanamivir treatment of whole blood cells from severe COVID-19 patients reduces host NEU-mediated shedding of cell surface sialic acid and neutrophil overactivation. These findings suggest that neuraminidase inhibitors can serve as host-directed interventions to dampen neutrophil dysfunction in severe infections. At a GlanceIn a severe systemic inflammatory response, such as sepsis and COVID-19, neutrophils play a central role in organ damage. Thus, finding new ways to inhibit the exacerbated response of these cells is greatly needed. Here, we demonstrate that in vitro treatment of whole blood with the viral neuraminidase inhibitors Oseltamivir or Zanamivir, inhibits the activity of human neuraminidases as well as the exacerbated response of neutrophils. In experimental models of severe sepsis, oseltamivir decreased neutrophil activation and increased the survival rate of mice. Moreover, Oseltamivir or Zanamivir ex vivo treatment of whole blood cells from severe COVID-19 patients rewire neutrophil function.

immunology↗