Immune requirements for protective Th17 recall responses to Mycobacterium tuberculosis challenge

• Published in: Mucosal immunology Vol. 8; no. 5; pp. 1099 - 1109
• Main Authors: Monin, L, Griffiths, K L, Slight, S, Lin, Y, Rangel-Moreno, J, Khader, S A
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2015; Elsevier Limited
• Subjects: 631/250/1619/554/1898/1273; 631/250/24/590; 631/250/255/1856; Allergology; Animals; Antibodies; Biomedical and Life Sciences; Biomedicine; Gastroenterology; Humans; Immunology; Interleukins - immunology; Mice; Mice, Knockout; Mycobacterium tuberculosis - immunology; Th1 Cells - immunology; Th17 Cells - immunology; Tuberculosis - immunology; Tuberculosis - prevention & control; Tuberculosis Vaccines - immunology; Tuberculosis Vaccines - pharmacology; Vaccines, DNA
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2014.136

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.