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

Abstract

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.

Nasal vaccination stimulates CD8+ T cells for potent protection against mucosal Brucella melitensis challenge

“…IL-22 was found to be dispensable for Fransicella tularensis 49 and Listeria monocytogenes 55 infections. However, IL-22 was important for recall responses to F. tularensis as demonstrated by its secretion by memory peripheral blood CD4 + and CD8 + T cells restimulated with F. tularensis Ags.…”

Inflammatory Monocyte Recruitment Is Regulated by Interleukin-23 during Systemic Bacterial Infection

“…The IL-23/IL-22/antimicrobial peptide axis has been shown to be important during extracellular bacterial infections with Citrobacter rodentium (47) and Klebsiella pneumoniae (1). Interestingly, although infection with L. monocytogenes induces IL-23-dependent production of IL-22, this cytokine is not necessary for bacterial clearance in the spleen or liver (12). In addition to the IL-23/IL-17/neutrophil and IL-23/IL-22/antimicrobial peptide pathways, our data uncover a novel IL-23/ monocyte pathway that protects against bacterial infection.…”

Interleukin-22 Reduces Lung Inflammation during Influenza A Virus Infection and Protects against Secondary Bacterial Infection

“…The early production of IL-22 by innate immune cells is crucial for host protective immunity to extracellular bacteria, including Klebsiella pneumoniae in the lung and Citrobacter rodentium in the intestine (32,33). On the other hand, IL-22 has no substantial role in host defense against Staphylococcus aureus, Mycobacterium tuberculosis, M. avium, Listeria monocytogenes, Candida albicans, or Schistosoma mansoni (34)(35)(36)(37). Of importance, IL-22 can provide protective innate immunity when the adaptive immune system is impaired.…”