Press releases
Please quote Nature Immunology as the source of these items.
The June 2007 issue of Nature Immunology is available online.
June 2007
New player in inflammatory 'shutdown'
Scientists show that a protein within immune cells stands poised to dampen inflammation, according to an article published this week online in Nature Immunology.
Inflammatory proteins are produced by immune cells following microbial infection. After clearance of the invading pathogen the inflammatory response must be switched off to avoid excessive damage to host tissues.
Tsuneyaso Kaisho and colleagues now demonstrate that a protein called PDLIM2 continuously targets the p65 subunit of the proinflammatory transcription factor NF-κB for destruction. PDLIM2 marks p65 for degradation and routes p65 into cellular compartments containing demolition machinery.
Consequently, mice lacking PDLIM2 suffer from lethal uncontrolled inflammation. These findings pinpoint another potential target for therapeutic efforts to suppress excessive inflammatory responses.
PDLIM2-mediated termination of transcription factor NF-κB activation by intranuclear sequestration and degradation of the p65 subunit
Takashi Tanaka, Michael J Grusby & Tsuneyasu Kaisho
Published online: 29 April 2007 | doi 10.1038/ni1464
Ancient diversity
An ancient enzyme drives diversification of immune receptors in lampreys, and resembles an enzyme with a similar function in mammals, according to a report published online this week in Nature Immunology.
Zeev Pancer and colleagues used computational analyses - 'genomic mining' - to look for molecular signatures in the lamprey genome. Clues to how lampreys diversify their antigen receptors, allowing them to combat any array of potential microbial threats, came from their identification of hundreds of short gene segments that encode bits of the antigen receptors. The authors also discovered evidence that these pieces can combine in almost an infinite array, thereby explaining how a diverse repertoire of receptors can be made.
The surprise the authors found in the lamprey genomic sequence was that these fish encode two enzymes similar to an enzyme called AID, which is essential for the production of different types of antibodies in mammals. In fact, further experiments performed in test tubes showed the lamprey enzymes can mutate target genes much like the mammalian AID enzyme. The new work suggests the ability to diversify antigen receptors occurred much earlier in evolution then previously thought and hence is an 'ancient adaptation'.
Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase
Igor B Rogozin, Lakshminarayan M Iyer, Lizhi Liang, Galina V Glazko, Victoria G Liston, Youri I Pavlov, L Aravind & Zeev Pancer
Published online: 29 April 2007 | doi 10.1038/ni1463
Blunting immunity by tuberculosis bacteria
A protein secreted by Mycobacterium tuberculosis — the bacterium that causes tuberculosis — significantly dampens early immune responses, reports a study to be published in the June issue of Nature Immunology. Infecting at least one-third of the world's population, this organism causes significant world-wide health problems, with new infections occurring at a rate of about one per second.
Joyoti Basu and colleagues evaluated the function of the secreted protein ESAT-6 — previously associated with inefficient immune responses to Mycobacterium tuberculosis — by showing that purified ESAT-6 blocks signaling from specialized immune receptor proteins known as Toll-like receptors. Key to that effect is the specific interaction of ESAT-6 with one of the Toll-like receptors, TLR2, on the surface of macrophages — important immune ‘sentry’ cells. The authors found that by binding to TLR2, ESTA-6 induces a signal that shuts down all other Toll-like receptor function.
Blockade of interactions between ESAT-6 and TLR2 might represent a therapeutic option for treating tuberculosis, while simulation of interactions between ESAT-6 and TLR2 may be useful in suppressing excessive inflammation.
Direct extracellular interaction between the early secreted antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in macrophages
Sushil Kumar Pathak, Sanchita Basu, Kunal Kumar Basu, Anirban Banerjee, Shresh Pathak, Asima Bhattacharyya, Tsuneyasu Kaisho, Manikuntala Kundu & Joyoti Basu
Published online: 7 May 2007 | doi 10.1038/ni1468
Immune responses tailored to specific pathogens
Yeast infection can stimulate the development of a unique type of immune cell, according to two articles to be published in the June issue of Nature Immunology.
Independent teams led by Caetano Reis e Sousa and Federica Sallusto studied immune responses, in mouse and human cells respectively, to the yeast Candida albicans — a ubiquitous pathogen that can cause life-threatening infections in immuno-compromised individuals. Both teams report strikingly complementary findings, that Candida albicans stimulates the development of T lymphocytes specialized in producing interleukin 17, an immuno-modulatory protein associated with both harmful autoimmunity and helpful immune responses to certain bacteria. Notably, the study by Sallusto and colleagues provides the first characterization of human interleukin 17-producing T lymphocytes.
These studied broaden our understanding of the ways that T lymphocytes can respond to pathogens, providing a key piece of the puzzle about interleukin 17 T cells, which likely play important roles in many immune responses.
Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17
Salomé LeibundGut-Landmann, Olaf Groß, Matthew J Robinson, Fabiola Osorio, Emma C Slack, S Vicky Tsoni, Edina Schweighoffer, Victor Tybulewicz, Gordon D Brown, Jürgen Ruland & Caetano Reis e Sousa
Published online: 22 April 2007 | doi 10.1038/ni1460
Another immune evasion strategy by HIV
Interaction of the human immunodeficiency virus (HIV) with dendritic cells--a specialized type of immune cell--circumvents immune activation and greatly enhances infection of T lymphocytes, reports a study to be published in the June issue of Nature Immunology.
Dendritic cells are required to initiate immune responses, and as targets of HIV infection, these cells are important contributors to HIV pathogenesis. Alison Simmons and colleagues evaluated the effect of HIV interaction with DC-SIGN, a protein receptor found largely on the surface of dendritic cells. HIV binding to DC-SIGN elicited a signaling pathway that prevented dendritic cells from actively stimulating subsequent immune responses. In addition, the authors show that HIV-DC-SIGN interaction can lead to transfer of virus to nearby T lymphocytes that then become infected leading to a burst of HIV production.
These results reveal how HIV can both evade dendritic cell immune activity and amplify its own replication. With nearly 40 million people world-wide currently living with HIV-AIDS, understanding the myriad ways that HIV can modulate immune responses is of paramount importance.
Activation of the lectin DC-SIGN induces an immature dendritic cell phenotype triggering Rho-GTPase activity required for HIV-1 replication
Ashleigh Hodges, Katherine Sharrocks, Mariola Edelmann, Dilair Baban, Arnaud Moris, Olivier Schwartz, Hal Drakesmith, Kay Davies, Benedikt Kessler, Andrew McMichael & Alison Simmons
Published online: 13 May 2007 | doi 10.1038/ni1470
