An obligatory anaerobic Salmonella�typhimurium strain redirects M2 macrophages to the M1 phenotype

Abstract

Abstract.A genetically engineered Salmonella typhimurium strain that may be applied in the medically useful therapeutic strategy of using bacterial agents to target breast cancer in a tumor-bearing nude mouse model has been previously reported. Furthermore, immune cell accumulation in breast tumor types has been observed, particularly distributed in regions surrounding the bacteria. M2 macrophages are associated with breast cancer aggressiveness, whereas M1 macrophages are prone to devouring bacteria and killing cancer cells. Therefore, this engineered tumor-targeting salmonella strain was used in an attempt to reverse the phenotype of M2 macrophages into the M1 phenotype. Subsequent to the co-culture of M2 macrophages with the bacteria for a short time, >50% of the M2 macrophages were invaded by bacteria. These M2 macrophages exhibited a decreased expression of mannose receptor (an M2 phenotypic marker) and increased expression of human leukocyte antigen-antigen D related (an M1 phenotypic marker). The results of the present study indicated that differentiated M2 macrophages may be redirected into the M1 phenotype following exposure to the engineered bacteria stimulus. This effect may be a potential mechanism by which bacteria retard tumor growth. Thus, this engineered bacterium may be a useful candidate for targeting and redirecting M2 macrophages into the M1 phenotype.

The Differential Phosphorylation-Dependent Signaling and Glucose Immunometabolic Responses Induced during Infection by Salmonella Enteritidis and Salmonella Heidelberg in Chicken Macrophage-like cells

“…Macrophages are present in many distinct tissues of the host, including the gut [ 25 , 26 ]. Macrophages are known to exist in two main states, the inflammatory state (M1) and the anti-inflammatory state (M2) [ 27 , 28 ]. Researchers have shown that the M1 state is closely associated with the upregulation and activation of glycolytic proteins, reactive oxygen species (ROS), and inflammatory cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL)-12, IL-17, etc.…”

Bacteria and macrophages in the tumor microenvironment

“…Some of the attenuated Salmonella strains and their derivatives used as drug carriers have also been tested in early clinical trials. A newly engineered Salmonella typhimurium strain called YB1 was reported to induce enhanced HLA-DR expression and reduced CD206 expression, and to remodel macrophages from the M2-to M1-polarized ( Yang et al, 2018 ). Additionally, heterologous flagellin from the bacterial pathogen Salmonella activates the TLR5 pathway and changes tumor-infiltrating macrophages into M1-polarized macrophages ( Chen et al, 2021 ).…”

Salmonella enterica and outer membrane vesicles are current and future options for cancer treatment

“…S. Typhimurium also induces tumor growth suppression from macrophages ( Kaimala et al., 2014 ); the macrophages are the main niche of this bacterium ( Yang et al., 2018 ). Macrophages are heterogeneous cells that play a central role in the antitumor efficacy of S. enterica .…”