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Role of beta-2 adrenergic receptor signaling in innate immunity against intracellular bacterial pathogens 2808

Year: 2025
Type: article
Abstract: Description Burkholderia thailandensis, an intracellular bacterium causing pneumonia, is a model for studying melioidosis due to its similarity to pathogenic mechanisms of highly virulent B. pseudomallei. The bacterium evades phagolysosome formation, proliferating within macrophages and leading to antibiotic-resistant infections. Lungs are densely innervated with sympathetic neurons that secrete neurotransmitter noradrenaline (NA) from their endings during homeostasis and inflammation/injury. NA acts on immune and non-immune cells in the lungs, mainly through β2-adrenergic receptors (β2-ARs). Our in vivo findings showed an increased hypothermia in β2-AR-deficient mice (Adrb2-/-) than in control mice after intranasal infection with B. thailandensis. These findings correlate with significant increased bacterial load recovery in the lungs, liver, and spleen of Adrb2-/- mice than the bacterial recovery in control mice at 24h of post-infection. Similarly, Adrb2-/- bone marrow-derived macrophages (BMDMs) co-cultured with B. thailandensis showed enhanced intracellular survival of bacteria than wild-type BMDMs infected with B. thailandensis. Additionally, treatment of infected wild-type BMDMs with β2-AR agonist significantly reduced the intracellular survival of bacteria. Our results suggest that the β2-AR signaling pathway protects against intracellular bacterial pathogens. Funding Sources Supported by National Institutes of Health (NIH) R35GM155117 and P20GM113117, American Heart Association (Transformational Project Award), and K-INBRE scholarship. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)
DOI: 10.1093/jimmun/vkaf283.689
Authors: Prabhu R. Joshi, Abigail Judd, Pankaj Baral
Language: English
Subfield: Epidemiology
Field: Medicine
Open Access status: bronze
OpenAlex ID: W4416446679
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