IL-23 is required for protection against systemic infection with Listeria monocytogenes

Karen D. Meeks, Amy N. Sieve, Jay K. Kolls, Nico Ghilardi, Rance E. Berg

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Listeria monocytogenes (LM) is a Gram-positive, intracellular bacterium that can induce spontaneous abortion, septicemia, and meningitis. Although it is known that neutrophils are required for elimination of the bacteria and for survival of the host, the mechanisms governing the recruitment of neutrophils to LM-infected tissues are not fully understood. We demonstrate here that IL-23 and the IL-17 receptor A (IL-17RA), which mediates both IL-17A and IL-17F signaling, are necessary for resistance against systemic LM infection. LM-infected IL-23p19 knockout (KO) mice have decreased production of IL-17A and IL-17F, while IFN-γ production is not altered by the lack of IL-23. LM induces the production of IL-17A from γδ T cells, but not CD4, CD8, or NK cells. Furthermore, a lack of efficient neutrophil recruitment to the liver is evident in both IL-23p19 KO and IL-17RA KO mice during LM infection. Immunocytochemical analysis of infected livers revealed that neutrophils were able to localize with LM in IL-23p19 KO and IL-17RA KO mice, indicating that IL-23 and IL-17RA do not regulate the precise localization of neutrophils with LM. The importance of IL-23-induced IL-17A was demonstrated by injecting IL-23p19 KO mice with recombinant IL-17A. These mice had reduced LM bacterial burdens compared with IL-23p19 KO mice that did not receive IL-17A. These results indicate that during LM infection, IL-23 regulates the production of IL-17A and IL-17F from γδ T cells, resulting in optimal liver neutrophil recruitment and enhanced bacterial clearance.

Original languageEnglish
Pages (from-to)8026-8034
Number of pages9
JournalJournal of Immunology
Volume183
Issue number12
DOIs
StatePublished - 15 Dec 2009

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