The inflammatory response and immune cell status following radiation exposure influence the host’s susceptibility to new infections 2306220

Abstract Introduction Tissue-targeted and whole-body irradiation (WBI) are widely used to treat patients with solid tumors and hematologic malignancies, respectively. Although medical countermeasures (MCMs) are in place to reduce the side effects of radiation exposure (RE), understanding how RE affects host immune status is critical to improve the protection against infection and sepsis. Methods We conducted a retrospective cohort study using the SlicerDicer™ tool to identify patients admitted to the University of Iowa Hospitals and Clinics (UIHC) from 2015 to 2025. Patients with a documented history of ionizing RE who later developed infection or sepsis were included; non-RE patients served as controls. For mouse studies, wild-type C57BL/6 mice were subjected to 0, 2, or 5Gy doses of WBI. Ten or more days after RE, mice received either lipopolysaccharide (LPS) or underwent cecal ligation and puncture (CLP) to induce sepsis. For infection studies, mice were challenged with Streptococcus pneumoniae or attenuated Listeria monocyogenes following RE. Results Patients with a history of RE exhibited a higher risk of developing infection, sepsis, and septic shock compared with non-RE controls. Although the incidence of infection and sepsis was highest shortly after RE, it declined over time. Interestingly, RE conferred WBI dose-dependent protection against two different LPS doses in mice, as reflected by improved control of pro-inflammatory cytokines compared with 0Gy mice. Notably, RE mice remained susceptible to polymicrobial CLP sepsis despite displaying inflammatory responses comparable to 0Gy mice. RE, also impaired cell-mediated immunity, thus failing to clear bacterial pathogens. While treatment with ampicillin at 12 hours post-infection improved survival, RE mice still exhibited defective pathogen clearance. Conclusion Thus, immune cellularity and inflammation control after RE determine the host’s ability to clear infection and improve survival. These findings help guide future work to improve MCMs for RE patients. Funding Source n/a Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)