Infection

Inflammatory dendritic cells migrate in and out of transplanted chronic mycobacterial granulomas in mice Schreiber, H. A. et al. J. Clin. Invest. 12 Sep 2011 (doi:10.1172/JCI45113)

During infection with Mycobacterium tuberculosis, host granulomas prevent bacterial dissemination, but little is known about the dynamics of adaptive immune activation during chronic mycobacterial infection. The authors fluorescently labelled dendritic cells (DCs), T cells and Mycobacterium bovis bacillus Calmette–Guérin, and transplanted acute or chronic liver granulomas from infected mice under the kidney capsule of wild-type syngeneic recipients. They found that monocyte-derived 'inflammatory' DCs of donor origin can egress from both chronic and acute granulomas to be replaced by recipient DCs and that this turnover occurs faster for chronic granulomas. DCs from acute and chronic granulomas disseminated to secondary lymphoid organs, and transferred antigen to lymph node-resident DCs to promote T cell priming. Thus chronic granulomas undergo continual immune surveillance.

T cells

T cell receptor internalization from the immunological synapse is mediated by TC21 and RhoG GTPase-dependent phagocytosis Martínez-Martín, N. et al. Immunity 35, 208–222 (2011)

Recognition of peptide–MHC complexes by T cell receptors (TCRs) leads to the formation of the immune synapse. This in turn initiates TCR signalling as well as TCR internalization, which is a means of controlling TCR stimulation. Here, the authors report that TCRs from the immune synapse are internalized through a phagocytic process, which is mediated by the GTPases TC21 and RHOG. First, they showed that T cells phagocytose TCR-binding beads, and TC21 and RHOG were essential for this. Second, they found that, following antigen binding, TC21- or RHOG-deficient T cells failed to internalize TCRs and initiate actin remodelling and were unable to take up peptide–MHC complexes from the APC membrane through the process of trogocytosis. Finally, they showed that TC21, which colocalizes with TCRs in the immune synapse, induces RHOG activation through phosphoinositide 3-kinase, and this was essential for the subsequent TCR internalization.

Innate immunity

Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity Guo, Y. et al. J. Exp. Med. 12 Sep 2011 (doi:10.1084/jem.20101568)

This study of a patient with an autosomal recessive form of complete Toll-like receptor 3 (TLR3) deficiency sheds light on the role of TLR3 in the response to viral double-stranded RNA. Previously described patients with autosomal dominant TLR3 deficiency — who have increased susceptibility to childhood herpes simplex virus 1 (HSV-1) encephalitis (HSE) but not to other viral infections — still have residual TLR3 responses, so it has been unclear whether TLR3 has a non-redundant role in antiviral innate immunity. Fibroblasts from the patient with autosomal recessive TLR3 deficiency had no response to the TLR3 agonist polyI:C and had an impaired interferon response to HSV-1, resulting in higher levels of viral replication and cell death. By contrast, peripheral blood mononuclear cells from the patient responded normally to polyI:C and to ten distinct viruses. This shows a non-redundant role for TLR3 in fibroblasts but a redundant role in circulating leukocytes, which provides an explanation for the absence of disseminated disease during HSE and the lack of increased susceptibility to other viral illnesses in TLR3-deficient patients.