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Listeria monocytogenes, a small gram-positive bacillus, causes sepsis and meningitis in immunocompromised patients and a devastating maternal/fetal infection in pregnant women. Recent outbreaks demonstrated that L. monocytogenes can cause gastroenteritis in otherwise healthy individuals and more severe invasive disease in immunocompromised patients. Centralized processing in the food industry may be the cause of these large-scale listeriosis outbreaks. The mouse model of listeriosis, which was developed in the 1960s, has been extraordinarily useful for studying T cell—mediated immunity. Contrary to the original concept that macrophages are the principal effector cells in listeriosis, we found that immigrating neutrophils play the predominant role in early liver defenses. At later time points, CD8+ T cells lyse infected hepatocytes by both perforin- and Fas-L/Fas—dependent mechanisms. Of interest, nonclassical major histocompatibility complex (MHC) class Ib—restricted cytolytic activity is expressed early during primary infection, whereas MHC class Ia—restricted activity is predominant through late primary and secondary infections.