Some long-term hospitalized patients with lung infections exhibit pathogen tolerance. To investigate whether long-term chronic infection can induce tolerance, we constructed a mouse model of pneumonia in which mice were infected once, twice, or three times with Acinetobacter baumannii. The results revealed that the inflammatory factor levels decreased in the lung lavage fluid and that pathological damage to the lung tissue was alleviated in the mice infected three times. Flow cytometry and transcriptome analysis of mouse lung tissue revealed that the expression of genes related to T cell activation, differentiation, and regulation and the proportion and number of regulatory T cells and immune suppression-related genes, such as Ctla4, Tigit, Slamf8, ICOS, and IDO1, were increased in mice infected three times. These findings show that repeated A. baumannii infections can induce tolerance, which may be mediated by immune suppression involving regulatory T cells.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.