Volume 14 Issue 12, December 2013

Various receptors alert cells to microbial invasion through the detection of conserved molecular patterns and initiate innate immunity. During infection with Legionella pneumophila, macrophages modulate cytokine responses by downregulating protein synthesis according to the pathogenic potential of the intruder.

Mice immunized with influenza virus in the presence of rapamycin, which blocks the formation of germinal centers, make mostly IgM antibodies that protect against infection with multiple subtypes of influenza virus, including avian viruses.

Inflammasomes are signaling platforms of the innate immune system that activate proinflammatory cytokines after microbial pathogens are sensed or sterile danger is detected. The kinases Syk and Jnk control inflammasome activation by mediating phosphorylation of the inflammasome adaptor ASC.

Precursor cells entering the thymus have non-T cell potential, yet T cell development is clearly favored. A mechanism dedicated to repressing conflicting myeloid cell fate early during the establishment of T cell identity has now been found.

Discriminating between harmless and pathogenic bacteria is a key challenge faced by the immune system. Ivanov and Roy demonstrate that virulent bacteria disrupt mTOR signaling, which then skews responses towards inflammatory cytokine production.

Type 2 innate lymphoid cells (ILC2 cells) provide early immune responses to helminthes and contribute to allergic inflammation. Singh and colleagues show that the transcription factor Gfi1 controls the development, activation and specification of ILC2 cells.

Induction of type I interferon is a central event of antiviral immune responses. Fikrig and colleagues show that the transcription factor ELF4 is recruited by STING and translocates to the nucleus to control transcription of type I interferon genes.

The adaptor ASC is required for caspase-1 activation via the NLRP3 and AIM2 inflammasomes. Mitsuyama and colleagues show that signaling dependent on the kinases Syk and Jnk controls ASC speck formation through ASC phosphorylation.

Antibody responses are impaired during HIV-1 infection. Cicala and colleagues show that the HIV-1 glycoprotein gp120 directly impairs B cell function by promoting expression of TGF-β and the inhibitory receptor FcRL4.

Influenza viruses are highly variable, which complicates vaccine strategies to protect against emerging viruses. McGargill and colleagues show that blocking the mTORC1 complex skews antibody responses to more conserved epitopes, thereby producing heterosubtypic protection.

Hematopoietic deficiency in the Notch target Hes1 results in severe defects in the T cell lineage. Bhandoola and colleagues show that Hes1 constrains myeloid gene-expression programs in T cell progenitors.

Jameson and colleagues show that the establishment of resident memory CD8⁺ T cells in nonlymphoid tissues requires transcriptional downregulation of the trafficking molecule S1P₁, mediated by induced loss of the transcription factor KLF2.

Long-lived tissue-resident memory T cells (T_RM cells) confer fast, robust protection after pathogen rechallenge. Gebhardt and colleagues show that skin T_RM cells arise from KLRG1^– cells that differentiate in situ in response to IL-15 and TGF-β.