Lymphocyte migration

Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids. Geissmann, F. et al. PLoS Biol. 3, e113 (2005)

Dan Littman and colleagues have used intravital fluorescence microscopy to look at the behaviour of natural killer T (NKT) cells in the liver, which comprise up to 30% of the lymphocytes found in this organ. NKT cells that were labelled with green fluorescent protein (GFP) — by replacing the gene encoding the chemokine receptor CXCR6 with cDNA encoding GFP — were shown to actively patrol the liver sinusoids without extravasating into the tissue, with a random motion that was independent of the direction of blood flow. The NKT cells underwent rapid arrest after activation through their T-cell receptor. The authors also looked at the role of CXCR6 expression by NKT cells, and they showed that this was required for cell survival but not for the crawling behaviour. This intravascular search for antigen by NKT cells is unprecedented for lymphocyte populations, which are normally sheltered in specialized compartments in the lymph nodes and spleen.

Dendritic cells

Immunological role of neuronal receptor vanilloid receptor 1 expressed on dendritic cells. Basu, S. & Srivastava, P. Proc. Natl Acad. Sci. USA 102, 5120–5125 (2005)

Vanilloid receptor 1 (VR1) is expressed by sensory neurons and has been shown to convey a sense of pain in response to capsaicin, a component of chillies. In support of the known overlap between neural and immune signalling pathways, this paper now shows that VR1 is also expressed by dendritic cells (DCs) and that receptor ligation can induce a pro-inflammatory response, involving the maturation of immature DCs in vitro and their migration to draining lymph nodes in vivo. In a T-cell-receptor-transgenic mouse model, the proliferation of ovalbumin-specific T cells in response to their cognate antigen was increased when capsaicin was injected with the antigen. It is therefore possible that other neuroactive ligands might also have immunological effects.

Infectious disease

Ipr1 gene mediates innate immunity to tuberculosis. Pan, H. et al. Nature 434, 767–772 (2005)

Only some individuals who are infected with Mycobacterium tuberculosis develop an active infection, and this innate susceptibility is thought to be genetically controlled. However, deciphering the genetic basis of susceptibility has proven challenging. Now, Pan et al. report the identification of a gene, intracellular-pathogen resistance 1 (Ipr1), that controls susceptibility to tuberculosis in mice. Ipr1 expression is lacking in susceptible macrophages, and these cells die by necrosis after infection. By contrast, Ipr1 is expressed by resistant macrophages, in which it is linked to the induction of apoptotic cell death following infection. Expression of Ipr1 also restricted replication of the bacterium Listeria monocytogenes, indicating that this could be a common innate defence mechanism against intracellular bacteria.