April 2024
Eosinophils potentiate anti-bacterial immunity
Article: Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity
Zhou J, Liu J, Wang B, et al
Signal Transduction and Targeted Therapy. 2024 February
Reviewed by Roopa Hebbandi Nanjundappa, MSc, PhD, Dalhousie University, Halifax, Canada
The generation of memory T cell responses against infections is considered a hallmark of protective immunity. The generation of CD8+ T cell memory relies on several factors including cytokine milieu in the microenvironment, initial CD4+ T cell responses, and the presence of macrophages (Cullen et al., 2019; Son et al., 2021; Lobby et al., 2022). Read more
The precise role of eosinophils in CD8+ T cell responses during infections has remained unclear. Therefore, a recent study by Zhou et al. aimed to elucidate the contribution of eosinophils to the generation of memory CD8+ T cell responses using an OVA-expressing Listeria monocytogenes (L.m) infection model via intraperitoneal injections. The study employed both in vitro culture techniques and a mouse model deficient in eosinophils (ΔdblGATA-1) to investigate the role of eosinophils in the generation of L.m-specific memory CD8+ T cells in spleen and mesenteric lymph nodes (MLNs). The findings revealed that eosinophils play a crucial role in enhancing the generation of CD8+ T cell memory to L.m infection, in the spleens but not in the MLNs, thereby providing resistance to reinfection in mice. Mechanistically, eosinophil-derived IL-4 was found to rescue L.m infection-induced JNK/Caspase-3 dependent apoptosis of CD8+ T cells, thus facilitating the establishment of immunological memory against bacterial infection. The involvement of IL-4 was confirmed through both in vitro culture assays and adoptive transfer experiments involving wildtype and IL-4 deficient eosinophils into ΔdblGATA-1 mice.
A major strength of the study lies in the authors' exploration of the previously undefined role of eosinophils in potentiating CD8+ T cell immunological memory in the context of L.m infection. Furthermore, this study opens up new questions: (1) Do transgenic IL-5 mice, which harbor increased eosinophil levels, show heightened CD8+ T cell immunological memory against L.m? (2) Does L.m. infection via oral routes induce similar memory in the gastrointestinal tract (GI), given that eosinophils are abundant in the GI tract lining? (3) Does a similar mechanism exist for other bacterial, viral, and fungal infections? (4) Are there any susceptibilities or compromises in patients receiving eosinophil-depleting therapies to secondary bacterial infections or responses to vaccinations?
Roopa Hebbandi Nanjundappa, MSc, PhD, is an AAI postdoctoral fellow at Dalhousie University. She earned her PhD in Immunology from the University of Calgary, where her research focused on understanding how a gut microbial molecular mimic of pancreatic beta-cell auto-antigen can protect the host from inflammatory bowel disease. Currently, she is investigating the roles of mast cells and eosinophils in Respiratory Syncytial Virus (RSV) infection under the mentorship of Dr. Jean Marshall.