Innate memory to bacterial infection

Abstract

The innate lymphoid cells (ILCs) ILC1, ILC2, and ILC3, which also includes the natural killer (NK) cells are important regulators and first line responder during pathogen invasion. The role of ILCs was evaluated using FACS sorting, cytokine production and surface markers analysis, cell depletion, heat killed bacterial immunisation and bacterial infection.

This study hypothesised that following immunisation mice would be able to restrain bacterial growth and aimed to investigate the magnitude and longevity and specificity of the response. Depletion of CD90+ cells resulted in the inability of mice to control bacterial infection whereas depletion of NK cells did not affect the control of bacterial infection. The burden of P. aeruginosa in mice immunised with heat killed P. aeruginosa and infected with live bacteria 10 days post immunisation was significantly lower on mice that received the immunisation showing a positive effect of vaccination.

The inability to control the bacterial infection was also observed in mice lacking ILCs; however, mice with ILCs also failed to completely clear the infection suggesting that ILCs alone are not able to maintain the protective response. Specificity was demonstrated here as mice immunised with P. aeruginosa and infected with either E. coli or S. aureus had higher counts of P. aeruginosa. Experiments in RAG1 knockout (Ko) mice lacking T and B cells, which received immunisation at different time points and infection on day 0 post immunisation led to an increased level of the proinflammatory cytokine IL-22. These results led to the conclusion that specific resistance to bacterial infection in mice through ILCs is possible and suggests the infection caused by P. aeruginosa caused activation of ILC3 subset, recruitment of neutrophils and other immune cells and production of IL-17 and IL-22 cytokines.

Date of Award	Dec 2021
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Government of Angola
Supervisor	Beckie Ingram (Supervisor) & Paul Moynagh (Supervisor)