IL-22 Production Is Regulated by IL-23 During Listeria monocytogenes Infection but Is Not Required for Bacterial Clearance or Tissue Protection

Listeria monocytogenes (LM) is a gram-positive bacterium that is a common contaminant of processed meats and dairy products. In humans, ingestion of LM can result in intracellular infection of the spleen and liver, which can ultimately lead to septicemia, meningitis, and spontaneous abortion. Interleukin (IL)-23 is a cytokine that regulates innate and adaptive immune responses by inducing the production of IL-17A, IL-17F, and IL-22. We have recently demonstrated that the IL-23/IL-17 axis is required for optimal recruitment of neutrophils to the liver, but not the spleen, during LM infection. Furthermore, these cytokines are required for the clearance of LM during systemic infection. In other infectious models, IL-22 induces the secretion of anti-microbial peptides and protects tissues from damage by preventing apoptosis. However, the role of IL-22 has not been thoroughly investigated during LM infection. In the present study, we show that LM induces the production of IL-22 in vivo. Interestingly, IL-23 is required for the production of IL-22 during primary, but not secondary, LM infection. Our findings suggest that IL-22 is not required for clearance of LM during primary or secondary infection, using both systemic and mucosal models of infection. IL-22 is also not required for the protection of LM infected spleens and livers from organ damage. Collectively, these data indicate that IL-22 produced during LM infection must play a role other than clearance of LM or protection of tissues from pathogen- or immune-mediated damage

Inflammatory monocyte recruitment is regulated by interleukin-23 during systemic bacterial infection

Listeria monocytogenes is a Gram-positive intracellular pathogen that causes meningitis and septicemia in immunocompro-mised individuals and spontaneous abortion in pregnant women. The innate immune response against L. monocytogenes is pri-marily mediated by neutrophils andmonocytes. Interleukin-23 (IL-23) is an important proinflammatory cytokine well known for its role in neutrophil recruitment in various infectious and autoimmune diseases. We have previously shown that IL-23 is required for host resistance against L. monocytogenes and for neutrophil recruitment to the liver, but not the spleen, during in-fection. Despite efficient neutrophil recruitment to the spleen, IL-23p19 knockout (KO)mice have an increased bacterial burden in this organ, suggesting that IL-23 may regulate the recruitment/function of another cell type to the spleen. In this study, we show that specific depletion of neutrophils abrogated the differences in bacterial burdens in the livers but not the spleens of C57BL/6 (B6) and IL-23p19 KOmice. Interestingly, L. monocytogenes-infected IL-23p19 KOmice had fewer monocytes in the spleen than B6mice, as well as a reduction in the monocyte-recruiting chemokines CCL2 and CCL7. Additionally, the overall concentrations of tumor necrosis factor alpha (TNF-) and nitric oxide (NO), as well as the percentages and total numbers of monocytes producing TNF- and NO, were reduced in IL-23p19 KOmice compared to levels in B6mice, leading to increased bacterial burdens in the spleens of L. monocytogenes-infected IL-23p19 KOmice. Collectively, our data establish that IL-23 is required for the optimal recruitment of TNF-- and NO-producing inflammatory monocytes, thus revealing a novel mecha-nism by which this proinflammatory cytokine provides protection against bacterial infection

Extracellular Superoxide Dismutase Enhances Recruitment of Immature Neutrophils to the Liver

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