Biology subjects

Baumann, Z.

Publications and source records attributed to Baumann, Z..

3 recordsLinked to original sources

bioRxiv2026

The brain-meningeal interface functions as a reservoir and entry site for brain parenchymal macrophages

Microglia are regarded as self-maintaining brain parenchymal macrophages without contribution from adult hematopoiesis. Nevertheless, peripheral macrophage engraftment into the brain has been reported, but the biological variables governing central nervous system (CNS) macrophage niche access remain unclear. We show that CNS macrophage engraftment is determined by the balance between tissue-resident macrophage (TRM) self-renewal and the temporal alignment of niche opening with the availability of engraftment-competent cells and proximity to the vacated niche, rather than prolonged niche vacancy. Fate mapping revealed that monocytes entering the subdural space undergo border-associated macrophage (BAM)-like differentiation, clonal expansion, and transpial migration into the parenchyma, whereas mature BAMs directly repopulate selectively vacated parenchymal niches. We further identify a parenchymal macrophage population with a peripheral BAM-like transcriptional program in aged and neurodegenerative human brains, challenging the dogma of MG-exclusivity. Together, these findings establish a predictive framework for interpreting macrophage maintenance and replacement and for developing macrophage-based therapies.

neuroscience↗

bioRxiv2026

Inhibition of the NLRP3 Inflammasome Prevents Hyperglycemia in a Humanized Rodent Model of Type 2 Diabetes

The NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome is a protein complex that senses metabolic disturbances and in response processes IL-1beta. Prolonged activation of the NLRP3 inflammasome by metabolic stress induces chronic low-grade inflammation and contributes to the development type 2 diabetes and its comorbidities. Here, we developed a mouse model of type 2 diabetes that features impaired proinsulin processing and the ability to form islet amyloid plaques, two determinants of human type 2 diabetes pathology. We show that at advanced ages, these mice develop amyloidosis and inflammation in their insulin-producing pancreatic islets. Beta-cell mass and function were impaired in these mice and severe hyperglycemia developed within 6 months. Oral application of OLT1177, a selective inhibitor of the NLRP3 inflammasome, prevented the development of hyperglycemia. Our data show that inhibition of the NLRP3 inflammasome in a humanized mouse model of severe type 2 diabetes prevents the development of amyloid-associated hyperglycemia.

Cell Biology↗

bioRxiv2019

Air pollution mediates diabetes by disrupting gut innate mucosal immunity

Air pollution has emerged as an unexpected risk factor for diabetes1-6. The mechanisms linking air pollution and diabetes remain, however, unknown. It has been postulated that lung exposure mediates diabetes via systemic inflammation and insulin resistance7-9. By contrast, gut exposure to pollutants has received little attention, even though a large proportion of air pollution particles are swallowed after mucociliary clearance from the upper airways10. Here, we identified intestinal macrophages as key mediators linking air pollutants with impaired beta-cell function. Upon oral exposure to air pollution, intestinal macrophages up-regulated inflammatory- and interferon-response pathways, which disrupted their normal differentiation towards an anti-inflammatory/resident phenotype. The resulting pro-inflammatory milieu in the gut impaired beta-cell identity and function via local cytokine secretion from macrophages as genetic and pharmacological macrophage or IL-1{beta} ablation protected mice from developing air pollution-induced diabetes. These data establish intestinal macrophage-derived cytokines as key mediators of air pollution associated beta-cell dysfunction, thus pointing towards novel therapeutic strategies.

immunology↗