How we protect ourselves against bacteria and fungi

Australian researchers have discovered the link between a specific gene and the T cells that help shield us against a variety of fungal and bacterial infections. Their research has been published in the Journal of Experimental Medicine.

The gene, STAT3, determines the development and function of important cells that bridge the gap between our fast-acting (innate) and slower-acting (adaptive) immune systems. People with mutations in the gene are prone to bacterial and fungal infections - particularly Staphylococcus aureus and Candida albicans.

While studying patients with STAT3 mutations, Garvan Institute researchers Dr Elissa Deenick and Associate Professor Stuart Tangye detected fewer numbers of two T cells which are major components of the immune system: natural killer T cells (NKT cells) and mucosal-associated invariant T cells (MAIT cells). These are unconventional T cells that do not behave like the specialist cells of the adaptive immune system; instead, they recognise specific pathogens and respond to them very rapidly.

NKT cells have evolved to recognise certain glycolipids, which are present in bacteria such as Sphingomonas and Ehrlichia. MAIT cells, meanwhile, recognise part of a vitamin B metabolite produced by a range of bacteria and fungi.

In healthy people, MAIT cells respond to any organism that produces the metabolite by pumping out messaging chemicals known as cytokines. In particular, they produce high levels of Interleukin 17 (IL-17), a cytokine known to be important in dealing with fungal infections.

The researchers found that patients with STAT3 mutations not only produce considerably fewer MAIT cells than normal, but the production of IL-17 by those cells is also reduced. The gene is therefore intrinsic to the ideal function of the cells.

“This is the first report to identify the STAT3 signalling pathway as non-redundant for maintenance of NKT and MAIT cells in healthy people,” said Associate Professor Tangye.

“In addition to being an important basic science finding, this knowledge expands the disease profile of patients with STAT3 mutations and will help in the development of better treatments.”

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