Fighting Malaria: Mosquitoes Know How

The mosquito fights malaria to the incidental benefit of humans. In this issue, Frolet et al. (2006) define states of “basal” and “induced” immunity and show that a single genetic manipulation can rid the mosquito of a noxious parasite

Intracellular Toll-like Receptors

Foreign nucleic acids, the signature of invading viruses and certain bacteria, are sensed intracellularly. The nucleic acid-specific Toll-like receptors (TLRs) detect and signal within endolysosomal compartments, triggering the induction of cytokines essential for the innate immune response. These cytokines include proinflammatory molecules produced mainly by macrophages and conventional dendritic cells, as well as type I interferons, which are produced in great quantities by plasmacytoid dendritic cells. The cellular and molecular pathways by which nucleic acids and TLRs meet within the endosome assure host protection yet also place the host at risk for the development of autoimmunity. Here, we review the latest findings on the intracellular TLRs, with special emphasis on ligand uptake, receptor trafficking, signaling, and regulation

Grasshopper Outlook on Rangelands: 2011

Grasshoppers are often found to be a significant problem for both farmers and ranchers. Even though grasshoppers are a normal component of a forage ecosystem and generally exert minimal disturbance, problems occur when conditions lead to grasshop¬per populations that increase to the point where they cause millions of dollars of damage. Grasshopper outbreaks are the result of a complex combination of factors. Several factors are beyond the control of managers. However, the “pasture microcli¬mate” (the immediate environment where grasshop¬pers hatch, grow, and reproduce) may be subject to subtle manipulation. Because grasshopper outbreaks are progressive and cumulative, small interruptions or reductions in the rates of metabolic processes may serve to reduce population expansion and consequent damage to vegetation. Spring weather plays a key role in the severity of outbreaks. Warm temperatures with little rainfall are favorable for the hatching and development of grasshoppers, while cool and wet conditions follow¬ing hatch are unfavorable to grasshopper growth and development. Surveyed grasshopper populations for 2010 are shown in fig. 1

Consequences of the recurrent MYD88 L265P somatic mutation for B cell tolerance

MYD88L265P has recently been discovered as an extraordinarily frequent somatic mutation in benign monoclonal IgM gammopathy, Waldenström's macroglobulinemia, and diffuse large B cell lymphoma. In this study, we analyze the consequences for antigen-activ

The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling

Toll-like receptors (TLRs) sense the presence of microbial and viral pathogens by signal transduction mechanisms that remain to be fully elucidated. A single point mutation (H412R) in the polytopic endoplasmic reticulum (ER)–resident membrane protein UNC93B abolishes signaling via TLR3, 7, and 9. We show that UNC93B specifically interacts with TLR3, 7, 9, and 13, whereas introduction of the point mutation H412R in UNC93B abolishes their interactions. We establish the physical interaction of the intracellular TLRs with UNC93B in splenocytes and bone marrow–derived dendritic cells. Further, by expressing chimeric TLRs, we show that TLR3 and 9 bind to UNC93B via their transmembrane domains. We propose that a physical association between UNC93B and TLRs in the ER is essential for proper TLR signaling

Expression of the Tumor Necrosis Factor Gene by Dermal Fibroblasts in Response to Ultraviolet Irradiation or Lipopolysaccharide

To examine the effects of different wavelengths of ultraviolet (UV) radiation on tumor necrosis factor (TNF) production, we took advantage of mice carrying a chloramphenicol acetyl transferase (CAT) reporter transgene bearing the entire TNF promoter and 3'-untranslated region. Aside from constitutive expression in the thymus, CAT activity was detected only in locally UVB- or UVC-irradiated skin. After UVB irradiation, markedly greater amounts of CAT activity were traced to the dermis rather than the epidermis; by contrast, almost all CAT activity was localized to the epidermis after UVC irradiation, Fibroblasts have not been shown previously to express the TNF gene, i.e., the TNF gene is highly methylated and inaccessible to exogenous modulation in 3T3 fibroblasts, However, the present report reveals that cultured dermal fibroblasts are capable of producing both CAT and TNF in response to treatment in vitro with either UVB irradiation, UVC irradiation, or lipopolysaccharide. These findings indicate that dermal fibroblasts may serve not only as a target for but also as a source of TNF