Nature Immunology pp 868 - 874

How the immune system may distinguish 'helpful' from 'harmful' bacteria is presented in the August issue of Nature Immunology. Not all bacteria are dangerous — on the contrary, the human gut is home to a wide variety of bacteria that help to maintain everyday intestinal health. When we unintentionally ingest harmful bacteria like salmonella, the immune system must detect the presence of a dangerous invader among a sea of friendly faces.

Shizuo Akira and colleagues show that immune cells expressing a receptor, TLR5, that recognizes a component of harmful bacteria, do not detect the helpful bacteria that normally reside in the gut. This is because these immune cells unexpectedly lack another receptor, TLR4, which can 'see' components present on both harmful and helpful bacteria. In this way, the immune system may be able to distinguish the good from the bad.

Nature Immunology pp 843 - 850

A unique type of skin-associated immune cell is 'instructed' during development to prevent harmful skin inflammation, according to a paper in the August issue of Nature Immunology.

Robert Tigelaar, Adrian Hayday and colleagues have identified an unusual strain of mice lacking these specialized skin cells, known as γδ⁺ lymphocytes. By comparing that 'defective' strain of mice with a normal one, Tigelaar and Hayday show that in the mice lacking these cells, an essential factor is missing from the thymus — an organ required for the development of many immune cells. That factor is needed to 'instruct' developing skin lymphocytes to develop into mature cells that can fight inflammation in the skin. These findings are important because until now it has not been clear if skin γδ⁺ lymphocytes require 'instruction' to become mature, protective cells.

Nature Immunology pp 835 - 842

A newly identified method deployed by viruses to escape the immune system is reported in the August issue of Nature Immunology. Many strategies devised by viruses to 'hide' or 'escape' have been devised and these results describe another, previously unknown mechanism.

Immune cells called natural killer T cells are important in detecting and containing herpes simplex virus 1 (HSV-1) infections, which cause cold sores. HSV-1 particles are 'displayed' on the surface of infected cells, enabling the natural killer T cells to distinguish between infected and uninfected cells. The molecule CD1d, which presents HSV-1 particles, constantly moves in a loop from the cell surface to the interior of the cell to sample and display of the contents of infected cells to natural killer T cells.

Peter Cresswell and colleagues demonstrate that HSV-1 blocks this loop; specifically preventing CD1d molecules from returning back to the cell surface. As a result, HSV-1-infected cells appear to be uninfected and are therefore nearly ‘invisible’ to natural killer T cells. Precisely how the virus blocks CD1d looping remains to be determined. However, these results emphasize an additional mechanism by which viruses can escape immune detection.