title: IL-23 is required for long-term control of Mycobacterium tuberculosis and B cell follicle formation in the infected lung.
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. tuberculosis-induced 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.
authors: Division of Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA. Shabaana.Khader@chp.edu
authors: Shabaana A
authors: SA
authors: Khader
authors: Lokesh
authors: L
authors: Guglani
authors: Javier
authors: J
authors: Rangel-Moreno
authors: Radha
authors: R
authors: Gopal
authors: Beth A Fallert
authors: BA
authors: Junecko
authors: Jeffrey J
authors: JJ
authors: Fountain
authors: Cynthia
authors: C
authors: Martino
authors: John E
authors: JE
authors: Pearl
authors: Michael
authors: M
authors: Tighe
authors: Yin-yao
authors: YY
authors: Lin
authors: Samantha
authors: S
authors: Slight
authors: Jay K
authors: JK
authors: Kolls
authors: Todd A
authors: TA
authors: Reinhart
authors: Troy D
authors: TD
authors: Randall
authors: Andrea M
authors: AM
authors: Cooper
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054382:Chemokine CXCL13 / Q000096:biosynthesis; D018858:Germinal Center / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D053759:Interleukin-23 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*
chemical_list: D054382:Chemokine CXCL13; C486386:Cxcl13 protein, mouse; D053759:Interleukin-23