Dataset Information

IL-22 Controls Iron-Dependent Nutritional Immunity Against Systemic Bacterial Infections

ABSTRACT: Host immunity limits iron availability to pathogenic bacteria, but whether immunity limits pathogenic bacteria from accessing host heme, the major source of iron in the body, remains unclear. Using Citrobacter rodentium, a mouse enteric pathogen and Escherichia coli, a major cause of sepsis in humans as models, we find that interleukin-22, a cytokine best known for its ability to promote epithelial barrier function, also suppresses the systemic growth of bacteria by limiting iron availability to the pathogen. Using an unbiased proteomic approach to understand the mechanistic basis of IL-22 dependent iron retention in the host, we have identified that IL-22 induces the production of the plasma hemoglobin scavenger haptoglobin and heme scavenger hemopexin. Moreover, the anti-microbial effect of IL-22 depends on the induction of hemopexin expression, while haptogloblin is dispensable. Impaired pathogen clearance in infected Il22-/- mice was restored by hemopexin administration and hemopexin-deficient mice had increased pathogen loads after infection. These studies reveal a previously unrecognized host defense mechanism regulated by IL-22 that relies on the induction of hemopexin to limit heme availability to bacteria leading to suppression of bacterial growth during systemic infections.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Plasma

SUBMITTER: Gabriel Nunez

LAB HEAD: Gabriel Nunez

PROVIDER: PXD005666 | Pride | 2017-02-03

REPOSITORIES: Pride

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IL-22 Controls Iron-Dependent Nutritional Immunity Against Systemic Bacterial Infections.

Sakamoto Kei K Kim Yun-Gi YG Hara Hideki H Kamada Nobuhiko N Caballero-Flores Gustavo G Tolosano Emanuela E Soares Miguel P MP Puente José L JL Inohara Naohiro N Núñez Gabriel G

Science immunology 20170203 8

Host immunity limits iron availability to pathogenic bacteria, but whether immunity limits pathogenic bacteria from accessing host heme, the major source of iron in the body, remains unclear. Using <i>Citrobacter rodentium</i>, a mouse enteric pathogen and <i>Escherichia coli</i>, a major cause of sepsis in humans as models, we find that interleukin-22, a cytokine best known for its ability to promote epithelial barrier function, also suppresses the systemic growth of bacteria by limiting iron a ...[more]

PMID: 28286877

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	UM_F_2015_0995.raw	Raw
	UM_F_2015_0995_1003NunezWTInfected.msf	Msf
	UM_F_2015_0996.raw	Raw
	UM_F_2015_0997.raw	Raw
	UM_F_2015_0998.raw	Raw