Citrobacter rodentium: Infection Mechanisms and Host Responses

Citrobacter rodentium is a gram-negative bacterium that serves as a model for studying gastrointestinal infections, particularly those caused by pathogenic Escherichia coli in humans. Understanding this bacterium’s infection mechanisms and the host’s response is important for developing treatments and preventive strategies against similar pathogens affecting human health.

This article explores how Citrobacter rodentium establishes infection within its host and examines the immune responses triggered to combat it.

Pathogenic Mechanisms

Citrobacter rodentium uses a sophisticated array of strategies to establish infection within its host. Central to its pathogenicity is the type III secretion system (T3SS), a molecular syringe-like apparatus that injects bacterial effector proteins directly into host cells. These effectors manipulate host cellular processes, facilitating bacterial adherence and colonization. The bacterium’s ability to form attaching and effacing (A/E) lesions on the intestinal epithelium is a hallmark of its infection strategy. These lesions result from the intimate attachment of the bacteria to the host cell surface, leading to the effacement of microvilli and disruption of normal cellular functions.

The bacterium’s arsenal includes the translocated intimin receptor (Tir), which is injected into host cells via the T3SS. Once inside, Tir integrates into the host cell membrane and serves as a receptor for the bacterial outer membrane protein intimin. This interaction is pivotal for the intimate adherence of Citrobacter rodentium to the host cells, promoting the formation of A/E lesions. Additionally, other effectors such as EspF and Map are involved in subverting host cell signaling pathways, enhancing bacterial colonization and persistence.

Host Immune Response

The interaction between Citrobacter rodentium and its host elicits a dynamic immune response, orchestrated primarily by the innate immune system. Upon detection of the pathogen, the intestinal epithelium and resident immune cells, such as macrophages and dendritic cells, initiate the defense process. These cells recognize pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRRs), such as Toll-like receptors. This recognition triggers a cascade of signaling events that lead to the production of pro-inflammatory cytokines and chemokines, which act as messengers to recruit additional immune cells to the site of infection.

As the inflammatory response unfolds, neutrophils are among the first responders, rapidly migrating to the infected tissues. These cells deploy various antimicrobial mechanisms, including the release of reactive oxygen species and antimicrobial peptides, to limit bacterial dissemination. Concurrently, adaptive immunity becomes engaged, with T-helper cells playing a central role in shaping the immune response. T-helper 17 (Th17) cells, in particular, are instrumental in the response against Citrobacter rodentium, as they secrete interleukin-17 (IL-17) and interleukin-22 (IL-22), which bolster mucosal defenses and enhance epithelial barrier function.