Macrophages from lupus-prone MRL mice have a conditional signaling abnormality that leads to dysregulated expression of numerous genes.

Macrophages (mϕ) from pre-diseased mice of the major murine inbred models of spontaneous autoimmunity (AI), including multiple lupus-prone strains and the type I diabetes-prone NOD (non-obese diabetic) strain, have identical apoptotic target-dependent abnormalities. This characteristic feature of mϕ from AI-prone mice suggests that abnormal signaling events induced within mϕ following their interaction with apoptotic targets may predispose to AI. Such signaling abnormalities would affect predominantly the processing and presentation of self-antigen (i.e., derived from apoptotic targets), while sparing the processing and presentation of foreign antigen (i.e., derived from non-apoptotic sources). Here, we used DNA microarrays to test the hypothesis that mϕ from AI-prone mice (MRL/MpJ [MRL/+] or MRL/MpJ-Tnfrsf6 ( lpr ) [MRL/lpr]) differentially express multiple genes in comparison to non-AI mϕ (BALB/c), but do so in a largely apoptotic cell-dependent manner. Mϕ were stimulated with lipopolysaccharide, a potent innate stimulus, in the presence or absence of serum (an experimental surrogate for apoptotic targets). In accord with our hypothesis, the number of genes differentially expressed by MRL mϕ was significantly increased in the presence vs. the absence of serum, the apoptotic target surrogate (n = 401 vs. n = 201). Notably, for genes differentially expressed by MRL mϕ in the presence of serum, serum-free culture normalized their expression to a level statistically indistinguishable from that by non-AI mϕ. Comparisons of mϕ from AI-prone NOD and non-AI C57BL/6 mice corroborated these findings. Together, these data support the hypothesis that mϕ from MRL and other AI-prone mice are characterized by a conditional abnormality elicited by serum lipids or apoptotic targets.

Genome Sequences of Six Cluster N Mycobacteriophages, Kevin1, Nenae, Parmesanjohn, ShrimpFriedEgg, Smurph, and SpongeBob, Isolated on Mycobacterium smegmatis mc2155.

The annotation of six cluster N Mycobacterium smegmatis phages (Kevin1, Nenae, Parmesanjohn, ShrimpFriedEgg, Smurph, and SpongeBob) reveals regions of genomic diversity, particularly within the central region of the genome. The genome of Kevin1 includes two orphams (genes with no similarity to other phage genes), with one predicted to encode an AAA-ATPase.

Eight Genome Sequences of Cluster BE1 Phages That Infect Streptomyces Species.

Cluster BE1 Streptomyces bacteriophages belong to the Siphoviridae, with genome sizes over 130 kbp, and they contain direct terminal repeats of approximately 11 kbp. Eight newly isolated closely related cluster BE1 phages contain 43 to 48 tRNAs, one transfer-messenger RNA (tmRNA), and 216 to 236 predicted open reading frames (ORFs), but few of their genes are shared with other phages, including those infecting Streptomyces species.

Genome Sequences of Mycobacteriophages Jane and Sneeze, New Members of Cluster G.

Jane and Sneeze are newly isolated phages of Mycobacterium smegmatis mc2155 from Hillsborough, NJ, and Palo Verde, Costa Rica, respectively. Both are cluster G, subcluster G1 mycobacteriophages. Notable nucleotide differences exist between genomes in the right half, including the presence of mycobacteriophage mobile element 1 (MPME1) in Jane.

Genome Sequence of Cluster W Mycobacteriophage Taptic.

The Taptic genome is the first to be annotated from the W cluster of mycobacteriophages infecting Mycobacterium smegmatis mc2155. All 92 predicted open reading frames (ORFs) and a single tRNA specifying glycine (tRNA-gly) are transcribed rightward. Many functionally uncharacterized ORFs appear to be W cluster specific, as nucleotide similarity is shared only with other W cluster genomes.

Genome Sequences of Chancellor, Mitti, and Wintermute, Three Subcluster K4 Phages Isolated Using Mycobacterium smegmatis mc2155.

Mycobacteriophages Chancellor, Mitti, and Wintermute infect Mycobacterium smegmatis mc2155 and are closely related to phages Cheetobro and Fionnbharth in subcluster K4. Genome sizes range from 57,697 bp to 58,046 bp. Phages are predicted to be temperate and to infect the pathogen Mycobacterium tuberculosis.

Altered cell-cell and cell-matrix interactions in the development of systemic autoimmunity.

MPhi of mice from the major inbred models of systemic lupus erythematosus (SLE) have an identical defect affecting the activity of the cytoskeletal regulator and G-protein Rho. This abnormality is triggered by apo cells. Strikingly, SLE-prone MPhi show normal Rho activity when cultured in the absence of apo cells. We used gene arrays to identify adhesion-related gene products that are abnormally expressed by MPhi from prediseased 4-6-week-old SLE-prone MRL mice in the presence of serum lipids mimicking apo cells (SL-Apo). MPhi of MRL mice differentially expressed 42 adhesion-related genes in the presence of SL-Apo. Of these, 32 were expressed normally in the absence of SL-Apo. As adhesive interactions play a major role in lymphocyte activation, the detected apo cell-dependent abnormality could predispose to the development of autoimmunity. Indeed, several recent genetic studies support a role for adhesion-related genes in the pathogenesis of chronic autoimmunity.