2025/08/29 by Kevin Eislmayr, Charlotte A. Nichols, Fitty L Liu +7 · 1 voice
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Medicine · #Escherichia coli research studies #Immune Response and Inflammation #Viral gastroenteritis research and epidemiology
paper · doi:10.1016/j.chom.2025.08.001
openalex publication_date 2025/08/29 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
Bacteria of the genus Shigella replicate in intestinal epithelial cells and cause shigellosis, a severe diarrheal disease that resolves spontaneously in most healthy individuals. During shigellosis, neutrophils are abundantly recruited to the gut and have long been thought to be central to Shigella control and pathogenesis. However, how shigellosis resolves remains poorly understood due to the longstanding lack of a tractable and physiological animal model. Here, using our newly developed Nlrc4 –/– Casp11 –/– mouse model of shigellosis, we unexpectedly find no major role for neutrophils in limiting Shigella or in disease pathogenesis. Instead, we uncover an essential role for macrophages in the host control of Shigella . Macrophages respond to Shigella via Toll-like receptors (TLRs) to produce IL-12, which then induces IFN-γ, a cytokine that is essential to control Shigella replication in intestinal epithelial cells. Collectively, our findings reshape our understanding of the innate immune response to Shigella .