IL-23 is required for long-term control of Mycobacterium tuberculosis and B cell follicle formation in the infected lung

Shabaana A. Khader, Lokesh Guglani, Javier Rangel-Moreno, Radha Gopal, Beth A. Fallert Junecko, Jeffrey J. Fountain, Cynthia Martino, John E. Pearl, Michael Tighe, Yin Yao Lin, Samantha Slight, Jay K. Kolls, Todd A. Reinhart, Troy D. Randall, Andrea M. Cooper

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

IL-23 is required for the IL-17 response to infection with Mycobacterium tuberculosis, but is not required for the early control of bacterial growth. However, mice deficient for the p19 component of IL-23 (Il23a -/-) exhibit increased bacterial growth late in infection that is temporally associated with smaller B cell follicles in the lungs. Cxcl13 is required for B cell follicle formation and immunity during tuberculosis. The absence of IL-23 results in decreased expression of Cxcl13 within M. tuberculosisinduced lymphocyte follicles in the lungs, and this deficiency was associated with increased cuffing of T cells around the vessels in the lungs of these mice. Il23a -/- mice also poorly expressed IL-17A and IL-22 mRNA. These cytokines were able to induce Cxcl13 in mouse primary lung fibroblasts, suggesting that these cytokines are likely involved in B cell follicle formation. Indeed, IL-17RA-deficient mice generated smaller B cell follicles early in the response, whereas IL-22-deficient mice had smaller B cell follicles at an intermediate time postinfection; however, only Il23a -/- mice had a sustained deficiency in B cell follicle formation and reduced immunity.We propose that in the absence of IL-23, expression of long-term immunity to tuberculosis is compromised due to reduced expression of Cxcl13 in B cell follicles and reduced ability of T cells to migrate from the vessels and into the lesion. Further, although IL-17 and IL-22 can both contribute to Cxcl13 production and B cell follicle formation, it is IL-23 that is critical in this regard.

Original languageEnglish
Pages (from-to)5402-5407
Number of pages6
JournalJournal of Immunology
Volume187
Issue number10
DOIs
StatePublished - Nov 15 2011

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