Bournazos, DiLillo, and Ravetch discuss the biology of Fc receptors and their contribution to the effector function of protective antibody responses during infections and in therapeutics.
Brief Definitive Report
Andersen et al. identify a novel genetic etiology of herpes encephalitis in an adult patient carrying a heterozygous loss-of-function mutation in the IRF3 gene. This mutation results in impaired INF production in response to viral infection
Phospholipase D2 drives mortality in sepsis by inhibiting neutrophil extracellular trap formation and down-regulating CXCR2
Lee et al. find that phospholipase D2 deficiency increases survival and decreases organ damage during experimental sepsis in mice which could be reversed with a CXCR2 antagonist. Thus, targeting PLD2 may offer therapeutics for septic patients.
Cha et al. use a phage display library screen to identify a peptide, P39, that binds to CD68 on the surface of Kupffer cells to inhibit malaria sporozoite cell entry. Thus, P39 may represent a therapeutic strategy for malaria by limiting hepatic infection.
While people infected with Leishmania can become refractory to reinfection, human vaccines have not yet been achieved. Glennie et al. identify a population of skin-resident Leishmania-specific memory T cells that produce IFN-γ and recruit circulating T cells to the skin in response to a subsequent parasitic infection. The findings indicate that a successful vaccine may be dependent on generating skin-resident memory T cells for an effective immune response.
Kindlin-3–mediated integrin adhesion is dispensable for quiescent but essential for activated hematopoietic stem cells
Ruppert et al. report that Kindlin-3–mediated integrin activation controls homing of hematopoietic stem cells (HSCs) to the bone marrow (BM) and the retention of activated, but not quiescent, HSCs in the BM niche.
FLT1 signaling in metastasis-associated macrophages activates an inflammatory signature that promotes breast cancer metastasis
Qian et al. show that the receptor tyrosine kinase FLT1 is highly expressed in a subset of macrophages enriched in breast cancer metastatic sites. Inhibition of this kinase reduces metastasis to the lungs by blocking signaling via focal adhesion kinase 1 to an inflammatory state in the macrophages centered on signaling from the macrophage growth factor, colony stimulating factor-1.
Interleukin 27R regulates CD4+ T cell phenotype and impacts protective immunity during Mycobacterium tuberculosis infection
Loss of IL-27R on T cells results in increased protection from Mycobacterium tuberculosis. Torrado et al. demonstrate that IL-27R−/− T cells show improved fitness that is associated with decreased expression of cell death molecules, maintenance of IL-2 production, and preferential accumulation in the lung parenchyma and around infected macrophages.
CNOT3 contributes to early B cell development by controlling Igh rearrangement and p53 mRNA stability
Inoue et al. report that CNOT3, a subunit of the CCR4–NOT deadenylase complex regulating mRNA decay and translational repression, controls Igh gene rearrangement and destabilizes the mRNA of the tumor suppressor p53. Loss of CNOT3 results in a block of pro- to pre–B cell transition.