Nature immunology
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Diseases preventable by underused vaccines cause the death of approximately 3 million children per year. The Global Alliance for Vaccines and Immunization (GAVI) was launched 10 years ago to tackle this appalling situation.
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Mucosal-associated invariant T lymphocytes (MAIT lymphocytes) are characterized by two evolutionarily conserved features: an invariant T cell antigen receptor (TCR) alpha-chain and restriction by the major histocompatibility complex (MHC)-related protein MR1. Here we show that MAIT cells were activated by cells infected with various strains of bacteria and yeast, but not cells infected with virus, in both humans and mice. ⋯ In the mouse, MAIT cells protected against infection by Mycobacterium abscessus or Escherichia coli. Thus, MAIT cells are evolutionarily conserved innate-like lymphocytes that sense and help fight off microbial infection.
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Toll-like receptor 4 (TLR4) signals the induction of transcription factor IRF3-dependent genes from the early endosome via the adaptor TRAM. Here we report a splice variant of TRAM, TAG ('TRAM adaptor with GOLD domain'), which has a Golgi dynamics domain coupled to TRAM's Toll-interleukin 1 receptor domain. After stimulation with lipopolysaccharide, TRAM and TAG localized to late endosomes positive for the GTPase Rab7a. ⋯ TAG displaced the adaptor TRIF from TRAM. TAG is therefore an example of a specific inhibitor of the adaptor MyD88-independent pathway activated by TLR4. Targeting TAG could be useful in the effort to boost the immunostimulatory effect of TLR4 without causing unwanted inflammation.
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Basophils, the least abundant granulocytes, have poorly understood functions. They have been linked to the development of T helper type 2 immunity during parasite infection and allergic inflammation. ⋯ However, distinctions must be made between what basophils 'can do' after in vitro manipulation and what they 'actually do' during in vivo immune responses; these may be very different. In this review, the functions of basophils determined on the basis of analysis of in vitro and in vivo systems and their potential involvement in clinical settings are discussed.