Case studies

Case study: development of novel ex vivo models (Prof. Marco Oggioni)

The discovery of bacterial replication within human macrophages prior to invasive disease onset has key implications for novel treatment options. Especially when understanding the pathogenesis of acute invasive infection and functional drug resistance.

We now have authorisation by the Health Research Authority and the Research Ethics Committee to explore these issues not only in porcine organs, sourced from the abattoir, but also in human spleens - normal spleens from partial pancreatectomy. This is a world-wide unique set-up which allows the study of early events during infection in the human organ responsible for our innate cell mediated immunity. Manuscript Ercoli et al 2018 and Chung et al.,2019.

Case study: Understanding how pollutants alter the behaviour of bacterial pathogens (Dr. Julie Morrissey)

Particle Matter (PM) enhances in vivo asymptomatic colonisation of the nasopharynx and invasion of the lower respiratory tract of the mouse by Streptococcus pneumoniae and Staphylococcus aureus, a remarkable discovery here at Leicester. Bacterial adherence and intracellular invasion of human respiratory epithelial cells were also augmented by PM. Academics at the university are now investigating whether PM increases invasion of epithelial cells by non-typable Haemophilus influenzae (NTHi).

Case study: Mycobacterium tuberculosis (LTBRG group)

Experimental mouse models of tuberculosis have been used to mechanistically investigate how an exemplar vertebrate host is capable of limiting mycobacterial infection. Such models have proven that activated interferon-gamma-secreting CD4+ T cells are required to stimulate infected macrophages to produce toxic oxygen and nitrogen radicals to kill mycobacteria.

A similar protective mechanism has been shown to function in the human immune response to mycobacterial infection. Since we know many of the molecular and cellular mechanisms involved in the murine protective immune response to mycobacterial infection, we can probe the evolution of immunity in the mouse lung using a low dose aerosol infection, which is analogous to human disease transmission but ensures that all mice become experimentally infected.

In order to inoculate between 30-50 bacteria into the lower airways, we have designed a sophisticated instrument that safely and reproducibly aerosolized a suspension of mycobacteria for delivery to up to 75 mice. This device is the foundation on which we investigate the mechanisms of organ-level expression of immunity, the cellular interactions on which immunity is based and molecular events that cooperatively kill viable mycobacteria.

Models typically involve mice at the pre-clinical research facility, where the animals are looked after by animal husbandry experts. All use of mice for experimentation is authorised on the basis that there is or will be substantial benefit. Animal welfare is at the forefront of all research at Leicester University and how each experiment will affect an animal is analysed both by research facilitators and the animal welfare experts.

Dr J Pearl, Dr Sarah Bugby and Professor John Lees are in the process of developing a 3D model of the mouse, in order, to teach students and staff about the physiology and anatomy of the mouse.