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Salmonella Typhimurium and inflammation: a pathogen-centric affair

Abstract

Microbial infections are controlled by host inflammatory responses that are initiated by innate immune receptors after recognition of conserved microbial products. As inflammation can also lead to disease, tissues that are exposed to microbial products such as the intestinal epithelium are subject to stringent regulatory mechanisms to prevent indiscriminate signalling through innate immune receptors. The enteric pathogen Salmonella enterica subsp. enterica serovar Typhimurium, which requires intestinal inflammation to sustain its replication in the intestinal tract, uses effector proteins of its type III secretion systems to trigger an inflammatory response without the engagement of innate immune receptors. Furthermore, S. Typhimurium uses a different set of effectors to restrict the inflammatory response to preserve host homeostasis. The S. Typhimurium–host interface is a remarkable example of the unique balance that emerges from the co-evolution of a pathogen and its host.

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Fig. 1: The type III protein secretion system.
Fig. 2: Model for the interaction of S. Typhimurium with the intestinal epithelium.
Fig. 3: Induction of proinflammatory and anti-inflammatory signalling pathways by S. Typhimurium.

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Acknowledgements

The author apologizes to many colleagues whose important work could not be discussed or cited due to space limitations. The author thanks M. Lara-Tejero for critical reading of the manuscript. Work in the author’s laboratory is supported by NIH grants R01AI114618, R01AI055472 and R01AI030492.

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Correspondence to Jorge E. Galán.

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Nature Reviews Microbiology thanks C. Bryant, A. Simmons and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Serovars

Types of Salmonella enterica based on their surface antigenic composition.

Innate immune receptors

Surface receptors in immune cells that can recognize conserved bacterial products and stimulate an inflammatory response.

Bacterial-associated molecular patterns

Conserved bacterial molecules that can stimulate innate immune receptors.

Dysbiosis

A condition in which the composition of the resident intestinal microbiota is altered in a manner that leads to disruption of intestinal physiology.

Type III secretion systems

(T3SSs). Complex molecular machines evolved by many bacterial pathogens to modulate host-cell processes through the delivery of bacterially encoded effector proteins directly into the target host cells.

Injectisomes

A name used to refer to the entire type III protein secretion nanomachine that injects effector proteins into host cells.

Flagella

A bacterial organelle that serves to propel the bacteria through liquid environments.

Salmonella pathogenicity island 1

(SPI-1). A discrete region of the Salmonella enterica genome that encodes several genes associated with pathogenesis, including one of its type III secretion systems.

Rho-family GTPases

A family of low molecular weight signalling proteins with intrinsic GTPase activity that regulate several cellular processes.

Macropinocytosis

A process by which cells can take up extracellular material.

Guanine nucleotide exchange factors

(GEFs). Proteins that can activate GTPases by stimulating the release of GDP to allow the binding of GTP.

Inflammasome

A cytoplasmic signalling platform that leads to the activation of caspase 1 or caspase 11 and the subsequent stimulation of inflammation.

Pyroptosis

A form of cell death that leads to inflammation.

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Galán, J.E. Salmonella Typhimurium and inflammation: a pathogen-centric affair. Nat Rev Microbiol (2021). https://doi.org/10.1038/s41579-021-00561-4

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