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Updated: Jan 1, 2026
Chronic Salmonella Infection Induced Intestinal Fibrosis
Published on: September 22, 2019
Salmonella-Driven Polarization of Granuloma Macrophages Antagonizes TNF-Mediated Pathogen Restriction during
Trung H M Pham1, Susan M Brewer1, Teresa Thurston2
1Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Abstract:
Many intracellular bacteria can establish chronic infection and persist in tissues within granulomas composed of macrophages. Granuloma macrophages exhibit heterogeneous polarization states, or phenotypes, that may be functionally distinct. Here, we elucidate a host-pathogen interaction that controls granuloma macrophage polarization and long-term pathogen persistence during Salmonella Typhimurium (STm) infection. We show that STm persists within splenic granulomas that are densely populated by CD11b+CD11c+Ly6C+ macrophages. STm preferentially persists in granuloma macrophages reprogrammed to an M2 state, in part through the activity of the effector SteE, which contributes to the establishment of persistent infection. We demonstrate that tumor necrosis factor (TNF) signaling limits M2 granuloma macrophage polarization, thereby restricting STm persistence. TNF neutralization shifts granuloma macrophages toward an M2 state and increases bacterial persistence, and these effects are partially dependent on SteE activity. Thus, manipulating granuloma macrophage polarization represents a strategy for intracellular bacteria to overcome host restriction during persistent infection.
Insights
Salmonella Typhimurium (STm) persists in M2-polarized macrophages within granulomas. Host tumor necrosis factor (TNF) signaling restricts this M2 polarization, limiting chronic STm infection.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Intracellular bacteria establish chronic infections within host granulomas.
- Macrophages within granulomas display diverse polarization states (phenotypes).
- These macrophage phenotypes may have distinct functional roles in infection.
Purpose of the Study:
- To investigate host-pathogen interactions controlling granuloma macrophage polarization.
- To understand mechanisms of long-term pathogen persistence during Salmonella Typhimurium (STm) infection.
- To identify host factors that regulate macrophage phenotypes in granulomas.
Main Methods:
- Analysis of STm infected splenic granulomas.
- Characterization of macrophage populations (CD11b+, CD11c+, Ly6C+).
- Assessment of macrophage polarization states (M2).
- Evaluation of the role of the bacterial effector SteE.
- Investigation of tumor necrosis factor (TNF) signaling pathways.
Main Results:
- STm preferentially persists in M2-polarized macrophages within splenic granulomas.
- The bacterial effector SteE contributes to M2 polarization and STm persistence.
- TNF signaling limits M2 polarization and restricts STm persistence.
- Neutralizing TNF promotes M2 polarization and increases bacterial persistence, partly via SteE.
Conclusions:
- Granuloma macrophage polarization is a key factor in controlling chronic STm infection.
- STm utilizes mechanisms, including SteE, to promote M2 polarization for persistence.
- Modulating TNF signaling impacts macrophage polarization and bacterial persistence.
- Targeting granuloma macrophage polarization offers a potential strategy against persistent intracellular bacterial infections.
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