Publication highlights

Children born with mutations in the ARPC5 protein, which is part of the internal cytoskeleton, experience immunodeficiency and a high risk of sepsis. Researchers at the Crick investigated immune system function in mice with and without ARPC5 mutations, observing inflammation in adult mice with ARPC5 deficiency that mirrored that in humans. They showed that this was due to a big change in bacterial composition in the gut after weaning, triggering intestinal inflammation, as giving antibiotics to ARPC5-deficient mice at a critical four-week time point fully prevented the disease from developing. Finally, the team showed that macrophages with ARPC5 mutations had lost their usual shape and could no longer kill bacteria effectively, leading to an overwhelming response to the microbiome.

Researchers at the Francis Crick Institute have discovered that a common dietary supplement could protect against chronic Cryptosporidium infections which are particularly prevalent in children under two and in areas with poorer sanitation. The researchers exposed mice to the Cryptosporidium parasite and observed that infection triggered an expansion of immune cells in the intestinal epithelium, which are part of the first line of defence against the parasite. When these CD8+ T cells were transferred to mice with weakened immune systems, the researchers saw that the mice were now able to fight off Cryptosporidium infection. Mice that lack the AHR receptor, or healthy mice fed a diet specifically deficient in indoles, had a reduced population of intestinal CD8+ T cells. This meant the mice were less able to fight off the infection, and showed that CD8+ T cells are reliant on the AHR system to protect the intestine.

As part of the CAPTURE study, researchers in collaboration with the National Institute for Health Research (NIHR) UCLH Biomedical Research Centre found that antibodies generated in people who had received only two doses of either the Oxford/AstraZeneca vaccine or the Pfizer/BioNTech vaccine were less able to neutralise the Omicron variant as compared to the Alpha and Delta variants. They also found that antibody levels dropped off in the first three months following the second dose but that a third ‘booster’ dose raised levels of antibodies that effectively neutralise the Omicron variant.

An example of our work on COVID-19 and of the flexible and collaborative nature of the Crick, involving several labs within the Crick and our collaborating universities and university hospitals. In this work, we described the discovery of pre-existing binding and neutralising antibodies against SARS-CoV-2 in uninfected and unexposed individuals. These antibodies, likely induced by exposure to seasonal coronaviruses, are present in a small percent of adults but in the majority of children, consistent with the relative sparing of the latter from the severe form of COVID-19