title: Immune requirements for protective Th17 recall responses to Mycobacterium tuberculosis challenge.
abstract: Tuberculosis (TB) vaccine development has focused largely on targeting T helper type 1 (Th1) cells. However, despite inducing Th1 cells, the recombinant TB vaccine MVA85A failed to enhance protection against TB disease in humans. In recent years, Th17 cells have emerged as key players in vaccine-induced protection against TB. However, the exact cytokine and immune requirements that enable Th17-induced recall protection remain unclear. In this study, we have investigated the requirements for Th17 cell-induced recall protection against Mycobacterium tuberculosis (Mtb) challenge by utilizing a tractable adoptive transfer model in mice. We demonstrate that adoptive transfer of Mtb-specific Th17 cells into naive hosts, and upon Mtb challenge, results in Th17 recall responses that confer protection at levels similar to vaccination strategies. Importantly, although interleukin (IL)-23 is critical, IL-12 and IL-21 are dispensable for protective Th17 recall responses. Unexpectedly, we demonstrate that interferon-γ (IFN-γ) produced by adoptively transferred Th17 cells impairs long-lasting protective recall immunity against Mtb challenge. In contrast, CXCR5 expression is crucial for localization of Th17 cells near macrophages within well-formed B-cell follicles to mediate Mtb control. Thus, our data identify new immune characteristics that can be harnessed to improve Th17 recall responses for enhancing vaccine design against TB.
authors: 1] Department of Pediatrics, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA [2] Department of Molecular Microbiology, Washington University School of Medicine in St Louis, St Louis, Missouri, USA.
authors: L
authors: L
authors: Monin
authors: Department of Molecular Microbiology, Washington University School of Medicine in St Louis, St Louis, Missouri, USA.
authors: K L
authors: KL
authors: Griffiths
authors: Department of Pediatrics, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: S
authors: S
authors: Slight
authors: Department of Pediatrics, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Y
authors: Y
authors: Lin
authors: Department of Medicine, Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, New York, USA.
authors: J
authors: J
authors: Rangel-Moreno
authors: 1] Department of Pediatrics, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA [2] Department of Molecular Microbiology, Washington University School of Medicine in St Louis, St Louis, Missouri, USA.
authors: S A
authors: SA
authors: Khader
mesh_terms: D000818:Animals; D006801:Humans; D007378:Interleukins / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology* / Q000494:pharmacology; D019444:Vaccines, DNA
chemical_list: D007378:Interleukins; C549320:MVA 85A; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA
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