Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens

Abstract

Infections by attaching and effacing (A/E) bacterial pathogens, such as Escherichia coli O157:H7, pose a serious threat to public health. Using a mouse A/E pathogen, Citrobacter rodentium, we show that interleukin-22 (IL-22) has a crucial role in the early phase of host defense against C. rodentium. Infection of IL-22 knockout mice results in increased intestinal epithelial damage, systemic bacterial burden and mortality. We also find that IL-23 is required for the early induction of IL-22 during C. rodentium infection, and adaptive immunity is not essential for the protective role of IL-22 in this model. Instead, IL-22 is required for the direct induction of the Reg family of antimicrobial proteins, including RegIIIbeta and RegIIIgamma, in colonic epithelial cells. Exogenous mouse or human RegIIIgamma substantially improves survival of IL-22 knockout mice after C. rodentium infection. Together, our data identify a new innate immune function for IL-22 in regulating early defense mechanisms against A/E bacterial pathogens.

Cytokines and effector T cell subsets causing autoimmune CNS disease

“…Thus, IL-22 modulates local tissue responses and targets cells of the skin, the digestive tract, the lungs and the kidney and promotes cell proliferation and differentiation, thereby enhancing host defence and wound-healing responses [113]. Moreover IL-22 exhibits protective functions by limiting tissue damage during inflammatory processes of the liver [114], the gut [115,116]and the myocardium [117]. The role of IL-22 in autoimmunity is not yet clear.…”

Regulation of the development of acute hepatitis by IL‐23 through IL‐22 and IL‐17 production

“…The proinflammatory/pathological nature is apparent in mouse models with diseases such as psoriasis [4] and rheumatoid arthritis [22], and T. gondii infection [11]. In contrast, IL-22 plays protective roles and has tissue-protective and antimicrobial properties in several mouse models with diseases such as inflammatory bowel disease (IBD) [23], hepatitis [24] and infection with invading pathogenic bacteria [10,25,26].…”

“…In infection with an attenuated strain of Salmonella enterica serovar Enteritidis, p19-deficient mice showed reduced survival and exacerbated liver necrosis only in the absence of IL-12 in an IL-17-independent manner [10]. In peroral infection with Toxoplasma gondii, which leads to the development of small intestine inflammation, the IL-23-dependent upregulation of IL-22 is essential for the development of ileitis; on the other hand, IL-17 is downregulated and dispensable [11].IL-22 is a member of the IL-10 cytokine family and plays important roles in inflammation, immune surveillance and tissue homeostasis [12][13][14][15] [10,25,26].Recently, we demonstrated that Notch, which is an evolutionally conserved molecule that controls cell fate decision in a variety of cells [27,28], drives IL-22 secretion by stimulating the AHR [29]. Mice that are deficient in RBP-J, a key mediator of Notch signaling, are highly susceptible to the detrimental immunopathology associated with Con A-induced hepatitis with little IL-22 production [29].…”

“…IL-22 is a member of the IL-10 cytokine family and plays important roles in inflammation, immune surveillance and tissue homeostasis [12][13][14][15] [10,25,26].…”

Microparticles released by Listeria monocytogenes-infected macrophages are required for dendritic cell-elicited protective immunity

“…As expected, the inoculation of Lm-infected macrophages into C57BL/6 mice strongly induced the production of IFN-c and IL-22 ( Figure 1c), two potent mediators of cellular inflammatory responses against bacterial pathogens. [19][20][21] In addition, IFN-c-producing CD4 1 T cells were analyzed by FACS and showed to be consistently present ( Figure 1d). This result was not due to the contamination of live Lm escaping from the infected macrophages, since the mice were treated with gentamicin before and after adoptive transfer.…”