Maintenance of Type IV Secretion Function During Helicobacter pylori Infection in Mice.

The type IV secretion system (T4SS) encoded on the pathogenicity island (PAI) secretes the CagA oncoprotein and other effectors into the gastric epithelium. During murine infection, T4SS function is lost in an immune-dependent manner, typically as a result of in-frame recombination in the middle repeat region of , though single nucleotide polymorphisms (SNPs) in or in other essential genes may also occur. Loss of T4SS function also occurs in gerbils, nonhuman primates, and humans, suggesting that it is biologically relevant and not simply an artifact of the murine model.

Unexpected Role of CD8 T Cells in Accelerated Clearance of Salmonella enterica Serovar Typhimurium from H-2 Congenic mice.

infection can cause gastroenteritis in healthy individuals or a serious, systemic infection in immunocompromised patients and has a global impact. CD4 Th1 cells represent the main lymphocyte population that participates in bacterial clearance during both primary and secondary infections in mice of the H-2 haplotype. Previous studies have used congenic mice to examine the function of major histocompatibility complex (MHC) molecules in elimination of this pathogen from the host.

Optimal protection against infection requires noncirculating memory.

While CD4 Th1 cells are required for resistance to intramacrophage infections, adoptive transfer of Th1 cells is insufficient to protect against infection. Using an epitope-tagged vaccine strain of , we found that effective protection correlated with expanded -specific memory CD4 T cells in circulation and nonlymphoid tissues. However, naive mice that previously shared a blood supply with vaccinated partners lacked T cell memory with characteristics of tissue residence and did not acquire robust protective immunity.

Collateral Damage: Detrimental Effect of Antibiotics on the Development of Protective Immune Memory.

Antibiotic intervention is an effective treatment strategy for many bacterial infections and liberates bacterial antigens and stimulatory products that can induce an inflammatory response. Despite the opportunity for bacterial killing to enhance the development of adaptive immunity, patients treated successfully with antibiotics can suffer from reinfection. Studies in mouse models of Salmonella and Chlamydia infection also demonstrate that early antibiotic intervention reduces host protective immunity to subsequent infection.

Salmonella Infection Enhances Erythropoietin Production by the Kidney and Liver, Which Correlates with Elevated Bacterial Burdens.

Salmonella infection profoundly affects host erythroid development, but the mechanisms responsible for this effect remain poorly understood. We monitored the impact of Salmonella infection on erythroid development and found that systemic infection induced anemia, splenomegaly, elevated erythropoietin (EPO) levels, and extramedullary erythropoiesis in a process independent of Salmonella pathogenicity island 2 (SPI2) or flagellin. The circulating EPO level was also constitutively higher in mice lacking the expression of signal-regulatory protein α (SIRPα).

Contaminated water delivery as a simple and effective method of experimental Salmonella infection.

Aim: In most infectious disease models, it is assumed that gavage needle infection is the most reliable means of pathogen delivery to the GI tract. However, this methodology can cause esophageal tearing and induces stress in experimental animals, both of which have the potential to impact early infection and the subsequent immune response.

Materials & Methods: C57BL/6 mice were orally infected with virulent Salmonella Typhimurium SL1344 either by intragastric gavage preceded by sodium bicarbonate, or by contamination of drinking water.

Rad7 E3 Ubiquitin Ligase Attenuates Polyubiquitylation of Rpn10 and Dsk2 Following DNA Damage in .

During Nucleotide Excision Repair (NER) in the yeast , ubiquitylation of Rad4 is carried out by the E3 ubiquitin ligase that includes Rad7-Elc1-Cul3 and is critical to optimal NER. Rad7 E3 activity targets Rad4 for degradation by the proteaseome but, in principle, could also trigger other DNA damage responses. We observed increased nuclear ubiquitin foci (Ub-RFP) formation in containing a Rad7 E3 ligase mutant () in response to DNA damage by benzo[a]pyrenediolepoxide (BPDE) in dividing cells.

Rad10-YFP focus induction in response to UV depends on RAD14 in yeast.

Rad14 is a DNA damage recognition protein in yeast Nucleotide Excision Repair (NER) and believed to function early in the cascade of events. The function of Rad14 presumably precedes that of the Rad1-Rad10 endonuclease complex, which functions in a downstream step incising DNA 5' to the site of DNA damage. We investigated whether recruitment of Rad10 to UV-induced DNA damage sites in live cells is dependent on Rad14 using fluorescence microscopy.