<scp>S</scp>almonella acquires ferrous iron from haemophagocytic macrophages

Nagy, Toni A.; Moreland, Sarah M.; Detweiler, Corrella S.

doi:10.1111/mmi.12739

Cited by 30 publications

(42 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hemophagocytosis was monitored by intracellular flow cytometry; macrophages that have engulfed erythrocytes stain positive for the erythrocyte marker TER119 (see Fig. S1 in the supplemental material) (23). At 18 h after infection with either bacterium, ca.…”

Section: Resultsmentioning

confidence: 99%

“…Confocal microscopy has identified S. Typhimurium within hemophagocytes in the liver from 1 to 8 weeks postinfection (20). These cells may be a survival niche for S. Typhimurium because they provide the bacteria with iron (23). In addition, hemophagocytes appear to have an alternatively activated phenotype (7,21,24), suggesting that they are less adept at killing pathogens than other kinds of macrophages (25).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Bacterial Stimulation of Toll-Like Receptor 4 Drives Macrophages To Hemophagocytose

et al. 2016

Self Cite

View full text Add to dashboard Cite

During acute infection with bacteria, viruses or parasites, a fraction of macrophages engulf large numbers of red and white blood cells, a process called hemophagocytosis. Hemophagocytes persist into the chronic stage of infection and have an anti-inflammatory phenotype. Salmonella enterica serovar Typhimurium infection of immunocompetent mice results in acute followed by chronic infection, with the accumulation of hemophagocytes. The mechanism(s) that triggers a macrophage to become hemophagocytic is unknown, but it has been reported that the proinflammatory cytokine gamma interferon (IFN-␥) is responsible. We show that primary macrophages become hemophagocytic in the absence or presence of IFN-␥ upon infection with Gram-negative bacterial pathogens or prolonged exposure to heat-killed Salmonella enterica, the Gram-positive bacterium Bacillus subtilis, or Mycobacterium marinum. Moreover, conserved microbe-associated molecular patterns are sufficient to stimulate macrophages to hemophagocytose. Purified bacterial lipopolysaccharide (LPS) induced hemophagocytosis in resting and IFN-␥-pretreated macrophages, whereas lipoteichoic acid and synthetic unmethylated deoxycytidine-deoxyguanosine dinucleotides, which mimic bacterial DNA, induced hemophagocytosis only in IFN-␥-pretreated macrophages. Chemical inhibition or genetic deletion of Toll-like receptor 4, a pattern recognition receptor responsive to LPS, prevented both Salmonella-and LPS-stimulated hemophagocytosis. Inhibition of NF-B also prevented hemophagocytosis. These results indicate that recognition of microbial products by Toll-like receptors stimulates hemophagocytosis, a novel outcome of prolonged Toll-like receptor signaling, suggesting hemophagocytosis is a highly conserved innate immune response.

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Bacterial Stimulation of Toll-Like Receptor 4 Drives Macrophages To Hemophagocytose

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Live Salmonella also induce the transformation of macrophages to hemophagocytes, these are phagocytes which have engulfed erythrocyte or leukocyte. In these cells, intracellular bacterial survival is greatly enhanced within hemophagocytes, due to a surplus of iron [47,48].…”

Section: Metal Starvation/toxicitymentioning

confidence: 99%

Hoodwinking the Big-Eater to Prosper: The Salmonella-Macrophage Paradigm

2018

View full text Add to dashboard Cite

Salmonella is a major cause of morbidity and mortality in the developing and underdeveloped nations. Being a foodborne disease, Salmonella infection is primarily contracted through the ingestion of contaminated food or water, or due to close contact with infected/carrier individuals. It is an intracellular pathogen, which can survive and replicate in various cells including macrophages, dendritic cells, epithelial cells, and other white blood cells. Once Salmonella crosses the intestinal barrier, it disseminates to various systemic sites by circulation via immune cells. One of the major cell types which are involved in Salmonella infection are host macrophages. They are the niche for intracellular survival and proliferation of Salmonella and a mode of dissemination to distal systemic sites. These cells are very crucial as they mediate the mounting of an appropriate innate and adaptive anti-Salmonella immune response. In this review, we have tried to concise the current knowledge of complex interactions that occur between Salmonella and macrophages.

show abstract

“…The bacteria reside within tissue macrophages (6,9) and hemophagocytic macrophages (10,56), which have phagocytosed intact erythrocytes and leukocytes. Recently, it has been observed that S. Typhimurium acquires iron from hemophagocytes (11).…”

mentioning

confidence: 99%

Increased Ferroportin-1 Expression and Rapid Splenic Iron Loss Occur with Anemia Caused by Salmonella enterica Serovar Typhimurium Infection in Mice

et al. 2015

Self Cite

View full text Add to dashboard Cite

e The Gram-negative intracellular bacterium Salmonella enterica serovar Typhimurium causes persistent systemic inflammatory disease in immunocompetent mice. Following oral inoculation with S. Typhimurium, mice develop a hematopathological syndrome akin to typhoid fever with splenomegaly, microcytic anemia, extramedullary erythropoiesis, and increased hemophagocytic macrophages in the bone marrow, liver, and spleen. Additionally, there is marked loss of iron from the spleen, an unanticipated result, given the iron sequestration reported in anemia of inflammatory disease. To establish why tissue iron does not accumulate, we evaluated multiple measures of pathology for 4 weeks following oral infection in mice. We demonstrate a quantitative decrease in splenic iron following infection despite increased numbers of splenic phagocytes. Infected mice have increased duodenal expression of the iron exporter ferroportin-1, consistent with increased uptake of dietary iron. Liver and splenic macrophages also express high levels of ferroportin-1. These observations indicate that splenic and hepatic macrophages export iron during S. Typhimurium infection, in contrast to macrophage iron sequestration observed in anemia of inflammatory disease. Tissue macrophage export of iron occurs concurrent with high serum concentrations of interferon gamma (IFN-␥) and interleukin 12 (IL-12). In individual mice, high concentrations of both proinflammatory (tumor necrosis factor alpha [TNF-␣])and anti-inflammatory (IL-10) cytokines in serum correlate with increased tissue bacterial loads throughout 4 weeks of infection. These in vivo observations are consistent with previous cell culture studies and suggest that the relocation of iron from tissue macrophages during infection may contribute to anemia and also to host survival of acute S. Typhimurium infection.T yphoid fever is acquired upon oral ingestion of food or water contaminated with Salmonella enterica serovar Typhi or Paratyphi and remains a serious threat to public health, especially in developing countries (1). Human typhoid fever causes a broad range of clinical signs, including splenomegaly, neuropathy, and hematopathology, such as cytopenias (2), that have been modeled in laboratory mice infected with Salmonella enterica serovar Typhimurium (3). Inbred mouse strains with differing genetic backgrounds are characterized as either sensitive or resistant to S. Typhimurium. Sensitivity to the intracellular bacterial infection is caused by genetic deficiencies in the innate or adaptive immune system (4, 5). For instance, mice lacking the cation transporter Nramp1 (Slc11a1), a regulator of cellular iron metabolism, are extremely sensitive to infection. Nramp1 ϩ mice are considered resistant to S. Typhimurium, because infection is generally nonfatal (6-8). Resistant mice infected by natural oral inoculation develop systemic infection with an acute hematopathological syndrome similar to that of humans with typhoid fever, including fever, anemia, inflammatory disease characterized by periph...

show abstract

Salmonella acquires ferrous iron from haemophagocytic macrophages

Cited by 30 publications

References 64 publications

Bacterial Stimulation of Toll-Like Receptor 4 Drives Macrophages To Hemophagocytose

Bacterial Stimulation of Toll-Like Receptor 4 Drives Macrophages To Hemophagocytose

Hoodwinking the Big-Eater to Prosper: The <b><i>Salmonella</i></b>-Macrophage Paradigm

Increased Ferroportin-1 Expression and Rapid Splenic Iron Loss Occur with Anemia Caused by Salmonella enterica Serovar Typhimurium Infection in Mice

Contact Info

Product

Resources

About