Foodborne salmonellosis is one of the most important bacterial zoonotic diseases worldwide. Salmonella Typhimurium is the serovar most frequently isolated from slaughter pigs in Europe. Circumvention of the host’s immune system by Salmonella might contribute to persistent infection of pigs. We found that Salmonella Typhimurium strain 112910a, which is able to persist in pigs, was capable of downregulating the expression of major histocompatibility class II (MHC II) molecules on porcine alveolar macrophages (PAM) in a Salmonella pathogenicity island 2 (SPI-2) dependent way and that MHC II downregulation was Salmonella strain dependent. The MHC II downregulation capacity was abolished when bacteria were opsonized with Salmonella-specific antibodies. Furthermore, intracellular proliferation of Salmonella Typhimurium opsonized with Salmonella positive pig serum was significantly impaired compared to that of the bacteria opsonized with negative pig serum. In a subsequent in vivo experiment, Salmonella Typhimurium strain MB2216 that did not induce MHC II downregulation in vitro, was shed less and persisted less but induced earlier seroconversion in pigs than strain 112910a. From the in vitro data, it is proposed that Salmonella Typhimurium downregulates the humoral immune response to promote intracellular survival inside porcine macrophages, contributing to long-term Salmonella persistence in pigs. The fact that the less persistent strain MB2216 induced earlier seroconversion than strain 112910a is of major interest for Salmonella-monitoring programs primarily based on serology, since this indicates that more persisting strains are more likely to escape serological detection
