Work

Fangchinoline drives NOS2-dependent host immunity to restrict intracellular enteric pathogens

Year: 2026

Type: article

Abstract: Intracellular bacterial infections remain difficult to treat due to antibiotic tolerance, immune evasion, and the emergence of multidrug resistance. Here, we identify Fangchinoline (Fcn), a natural alkaloid, as a host-directed immunomodulator that restricts intracellular Salmonella through NOS2-dependent nitric oxide (NO) signalling. Fcn enhances macrophage bactericidal activity and promotes Th1 immunity, leading to improved bacterial control in vitro and in vivo . Pharmacological inhibition of NO synthesis and loss of protection in NOS2 −/− mice establish NO as a central effector mechanism. Serum metabolomics indicate Fcn is associated with immunometabolic changes consistent with enhanced NO biosynthesis. In addition, Fcn synergizes with suboptimal-dose Ciprofloxacin to control Salmonella infection while preserving host immune responses. Notably, Fcn primes memory-like T cell responses and enhances resistance upon subsequent infection. Collectively, these findings suggest Fangchinoline as a host-directed immunotherapeutic that integrates metabolic, innate, and adaptive immune programs to restrict intracellular enteric pathogens, including multidrug-resistant strains, and augment antibiotic efficacy.

Source: iScience

DOI: 10.1016/j.isci.2026.116940

Authors: Srikanth Sadhu, Rajdeep Dalal, Sonu Kumar Gupta, Yashwant Kumar, Deepak Kumar Rathore, Amit Awasthi

Institution: Translational Health Science and Technology Institute

Language: English

Topic: Immune Response and Inflammation

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,240