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Toll-like receptor (TLR) signaling activates the transcription factor NF-κB and production of proinflammatory cytokines. O'Neill and colleagues show that TLR signaling induces the microRNA miR-21 to dampen PDCD4 expression, which leads to less NF-κB activity and more IL-10 production.
B cell development requires interleukin 7 signals that activate the transcription factor STAT5. Busslinger and colleagues report that STAT5 has a permissive rather than instructive role in pro-B cell survival and immunoglobulin recombination.
Naive CD4+ T cells can differentiate into distinct polarized effector cells, but detailed characterization of physiologic CD4 memory is lacking. Jenkins and colleagues show that TH1 and TH17 memory cells differ in longevity and arise via different infection routes.
Production of mature interleukin 1β (IL-1β) requires Il1b transcription and inflammasome-mediated processing of IL-1β protein. Ruland and colleagues show that the RNA virus sensor RIG-I signals via the adaptors CARD9 and Asc to facilitate both processes.
TLR4 signals via MyD88 and TRIF to activate proinflammatory cytokine and type I interferon responses. Karin and colleagues show that different ubiquitination of TRAF3 via K48 or K63 dictates the ensuing immune response.
Autophagy facilitates host defense against invading bacteria. Philpott and colleagues show that Nod1 and Nod2 link pathogen sensing to autophagy by recruiting the autophagy protein AGT16L1 to the site of pathogen entry.
High-affinity and isotype-switched antibodies arise from germinal center reactions. Goodnow and colleagues identify the Rho guanine nucleotide–exchange factor DOCK8 as being essential for sustained B cell immune synapse formation in germinal centers and mature antibody responses.
Mammalian cells ubiquitinate bacteria that erroneously enter the cytosol and target these intruding microbes for destruction by autophagy. New work shows that the protein NDP52 directly binds to ubiquitinated bacteria and facilitates the assembly of an autophagic membrane that surrounds these invaders.
Regulatory T cells that express the transcription factor Foxp3 are pivotal in suppressing autoimmune responses. A report in this issue describes a key role for interleukin 10 produced by lamina propria macrophages in maintaining Foxp3 expression during inflammatory responses in the intestine.
The induction of type I interferon is a critical checkpoint in antiviral immunity. Toll-like receptor 2 can unexpectedly induce type I interferon in the subset of inflammatory monocytes during infection with vaccinia virus.
Peptides able to positively select major histocompatibility complex class II–restricted thymocytes have not yet been defined. Two new reports identify and ascribe important extrathymic functions to several positively selecting peptides for CD4+ T cells.
Ariadne is the legendary Minoan goddess of the Labyrinth. The term 'Ariadne's thread' is used to describe the understanding of complex issues. Immunologists attending the 5th Leukocyte Signal Transduction Workshop discussed the Ariadne's thread woven about intracellular signaling pathways.
The mitochondrial adaptor MAVS is necessary for the transmission of RIG-I and Mda5 antiviral signals. Jiang and colleagues show that PCBP2 negatively regulates MAVS stability by recruiting the L48-ubiquitinating enzyme AIP4, thereby preventing excessive cytokine responses.
The molecular mediators responsible for directing T helper type 2 (TH2) differentiation remain incompletely defined. Dong and co-workers find that the transcription factor Dec2 promotes expression of the transcription factor JunB and is essential for the induction of TH2 responses.
Nod2 senses intracellular bacteria and is required for their eradication. Nuñez and co-workers now describe a T cell–intrinsic role for Nod2 in combating the intracellular parasite Toxoplasma gondii.
Immunization elicits B cell memory and short- and long-term antibody-secreting plasma cells. Weill and colleagues show that long-term IgM+ and IgG+ memory B cells can persist in germinal centers and undergo different fates after antigenic rechallenge.
Defensins combat pathogenic bacteria invading the mammalian intestine. Salzman and co-workers find that defensins influence the composition of the small intestinal commensal microbiota and the presence of interleukin 17–producing T cells in the lamina propria.