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Updated: Apr 14, 2026
High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages
Published on: August 11, 2014
Replication of Salmonella enterica Serovar Typhimurium in Human Monocyte-Derived Macrophages
Stephanie K Lathrop1, Kelsey A Binder1, Tregei Starr1
1Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Abstract:
Salmonella enterica serovar Typhimurium is a common cause of food-borne gastrointestinal illness, but additionally it causes potentially fatal bacteremia in some immunocompromised patients. In mice, systemic spread and replication of the bacteria depend upon infection of and replication within macrophages, but replication in human macrophages is not widely reported or well studied. In order to assess the ability of Salmonella Typhimurium to replicate in human macrophages, we infected primary monocyte-derived macrophages (MDM) that had been differentiated under conditions known to generate different phenotypes. We found that replication in MDM depends greatly upon the phenotype of the cells, as M1-skewed macrophages did not allow replication, while M2a macrophages and macrophages differentiated with macrophage colony-stimulating factor (M-CSF) alone (termed M0) did. We describe how additional conditions that alter the macrophage phenotype or the gene expression of the bacteria affect the outcome of infection. In M0 MDM, the temporal expression of representative genes from Salmonella pathogenicity islands 1 and 2 (SPI1 and SPI2) and the importance of the PhoP/Q two-component regulatory system are similar to what has been shown in mouse macrophages. However, in contrast to mouse macrophages, where replication is SPI2 dependent, we observed early SPI2-independent replication in addition to later SPI2-dependent replication in M0 macrophages. Only SPI2-dependent replication was associated with death of the host cell at later time points. Altogether, our results reveal a very nuanced interaction between Salmonella and human macrophages.
Insights
Salmonella Typhimurium replication in human macrophages depends on cell phenotype. M1 macrophages prevent bacterial growth, while M2a and M0 macrophages permit Salmonella Typhimurium replication, influencing infection outcomes.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Salmonella Typhimurium causes foodborne illness and bacteremia in immunocompromised individuals.
- Bacterial systemic spread in mice relies on macrophage infection and replication.
- Replication of Salmonella Typhimurium within human macrophages is not well understood.
Purpose of the Study:
- To investigate the capacity of Salmonella Typhimurium to replicate in human macrophages.
- To determine how macrophage phenotype influences Salmonella Typhimurium replication.
- To explore the roles of Salmonella pathogenicity islands (SPI1 and SPI2) and the PhoP/Q system in human macrophage infection.
Main Methods:
- Primary human monocyte-derived macrophages (MDM) were differentiated into distinct phenotypes (M1, M2a, M0).
- MDM were infected with Salmonella Typhimurium to assess bacterial replication.
- Gene expression of Salmonella pathogenicity islands (SPI1, SPI2) and the PhoP/Q system were analyzed.
- Host cell death was monitored in relation to bacterial replication.
Main Results:
- Macrophage phenotype significantly impacts Salmonella Typhimurium replication: M1 macrophages inhibited growth, while M2a and M0 macrophages supported it.
- In M0 macrophages, early SPI1-independent and later SPI2-dependent replication occurred.
- In contrast to mouse models, early replication in M0 macrophages was SPI2-independent.
- Later, SPI2-dependent replication was associated with host cell death.
Conclusions:
- Human macrophage phenotype critically dictates Salmonella Typhimurium replication.
- Salmonella Typhimurium exhibits distinct replication dynamics in human macrophages compared to mouse models.
- The interaction between Salmonella and human macrophages is complex and phenotype-dependent, with implications for disease pathogenesis.
