BCG vaccination drives accumulation and effector function of innate lymphoid cells in murine lungs

Abstract

The tuberculosis (TB) vaccine bacille Calmette-Guérin (BCG) prevents disseminated childhood TB; however, it fails to protect against the more prevalent pulmonary TB. Limited understanding of the immune response to Mycobacterium tuberculosis, the causative agent of TB, has hindered development of improved vaccines. Although memory CD4 T cells are considered the main mediators of protection against TB, recent studies suggest there are other key subsets that contribute to antimycobacterial immunity. To that end, innate cells may be involved in the protective response. In this study, we investigated the primary response of innate lymphoid cells (ILCs) to BCG exposure. Using a murine model, we showed that ILCs increased in number in the lungs and lymph nodes in response to BCG vaccination. Additionally, there was significant production of the antimycobacterial cytokine IFN-γ by ILCs. As ILCs are located at mucosal sites, it was investigated whether mucosal vaccination (intranasal) stimulated an enhanced response compared to the traditional vaccination approach (intradermal or subcutaneous). Indeed, in response to intranasal vaccination, the number of ILCs, and IFN-γ production in NK cells and ILC1s in the lungs and lymph nodes, were higher than that provoked through intradermal or subcutaneous vaccination. This work provides the first evidence that BCG vaccination activates ILCs, paving the way for future research to elucidate the protective potential of ILCs against mycobacterial infection. Additionally, the finding that lung ILCs respond rigorously to mucosal vaccination may have implications for the delivery of novel TB vaccines.

Innate lymphoid cells in lung infection and immunity

“…This effect was even more pronounced when IL‐10 signaling was inhibited by anti‐IL‐10R treatment. A recent study further identified an accumulation of ILC1 (Lin − CD90.2 + CD127 + IL‐17RB − IL‐23R − NKp46 + ), ILC2 (Lin − CD90.2 + CD127 + IL‐17RB + ) and ILC3 (Lin − CD90.2 + CD127 + IL‐17RB − IL‐23R + NKp46 +/− ) in the lungs along with enhanced IFN‐γ production after different routes of BCG vaccination . A more thorough analysis of the ILC subsets, including characterization using transcription factors would help to gain clear evidence for the involvement of ILCs in M. tuberculosis infection.…”

Immunology & Cell Biology's top 10 original research articles 2017–2018

“…Steigler et al . BCG vaccination drives accumulation and effector function of innate lymphoid cells in murine lungs Barnes & Cyster.…”

“…Another key topic covered in our top 10 publications is the identification and characterization of innate and innate‐like lymphocytes including innate lymphoid cells (ILC), mucosal‐associated invariant T (MAIT) cells, and natural killer T (NKT) cells . The study by Steigler et al .…”

“…The study by Steigler et al . reveals a role for lung ILC in inducing γ‐interferon (IFN‐γ) production after mucosal BCG vaccination and highlights a new pathway to target to enhance antimycobacterial protection . Taking a more fundamental approach, Zinser et al .…”

“…3 Using CCR2 À/À animals, which only manifested a reduced inflammatory monocyte recruitment in the lungs after respiratory vaccinia virus infection, Desai et al investigated not only the short-term impact but also the longterm consequence of the absence of inflammatory monocytes and reported a significant impairment in the long-term maintenance but not generation of the CXCR3 hi CX3CR1 lo CD8 T RM -cell subset. 3 Another key topic covered in our top 10 publications is the identification and characterization of innate and innatelike lymphocytes including innate lymphoid cells (ILC), 4 mucosal-associated invariant T (MAIT) cells, 6 and natural killer T (NKT) cells. 7 The study by Steigler et al reveals a role for lung ILC in inducing c-interferon (IFN-c) production after mucosal BCG vaccination and highlights a new pathway to target to enhance antimycobacterial protection.…”