Salmonella isolates that lack or overproduce DNA adenine methylase (Dam) elicited a cross-protective immune response to different Salmonella serovars. The protection afforded by the Salmonella enterica serovar Typhimurium Dam vaccine was greater than that elicited in mice that survived a virulent infection. S. enterica serovar Typhimurium Dam mutant strains exhibited enhanced sensitivity to mediators of innate immunity such as antimicrobial peptides, bile salts, and hydrogen peroxide. Also, S. enterica serovar Typhimurium Dam ؊ vaccines were not immunosuppressive; unlike wild-type vaccines, they failed to induce increased nitric oxide levels and permitted a subsequent robust humoral response to diptheria toxoid antigen in infected mice. Dam mutant strains exhibited a low-grade persistence which, coupled with the nonimmunosuppression and the ectopic protein expression caused by altered levels of Dam, may provide an expanded source of potential antigens in vaccinated hosts.Many pathogenic bacterial species are composed of multiple strains (serotypes) that can cause disease in animal hosts vaccinated against only a single pathogenic strain. Thus, it is desirable to develop bacterial vaccines that can stimulate crossprotective host immune responses to several pathogenic strains. Much of the work regarding the construction of live bacterial vaccines has been performed with Salmonella spp. since they establish an infection by direct interaction with the gut-associated lymphoid tissue, resulting in strong mucosal responses. Salmonella spp. also invade and proliferate within host cells and thus are capable of eliciting strong cell-mediated immune responses (9,20,23,39).Conceptually, cross-protective immunity could be elicited by live vaccines that express multiple antigens. The rationale is that although different serotypes possess different antigen repertoires, some of the protective antigens may be shared among heterologous serotypes and that expression of these shared antigens may lead to cross-protective immunity. We have recently shown that Salmonella DNA adenine methylase (Dam) mutants ectopically express multiple genes that are normally induced during infection (18). These Dam mutants are markedly attenuated but highly effective as live vaccines against Salmonella infection of mice (12, 18) MATERIALS AND METHODSBacterial strains and phage. Salmonella enterica serovar Typhimurium strains used in this study (Table 1) were derived from strain ATCC 14028 (CDC 6516-60). Strains used in infection studies were grown overnight in Luria broth (LB) at 37°C with shaking. The dam-102::Mud-Cm allele was obtained from John Roth and transduced into virulent S. enterica serovar Typhimurium strain 14028 and S. enterica serovar Enteritidis O1,9,12; CDC SSU7998, obtained from the Salmonella Genetic Stock Center, SARB, #16 (3, 36), resulting in the Dam Ϫ strain, MT2223. S. enterica serovar Dublin Lane was obtained from Don Guiney (6). The construction of S. enterica serovar Typhimurium dam⌬232 (MT2188) was described previously (18)...

The reduced efficiency of the mammalian immune system with aging increases host susceptibility to infectious and autoimmune diseases. However, the mechanisms responsible for these pathologic changes are not well understood. In this study, we demonstrate that the bone marrow, blood, and secondary lymphoid organs of healthy aged mice possess increased numbers of immature myeloid cells that are phenotypically similar to myeloid-derived suppressor cells found in lymphoid organs of mice with progressive tumors and other pathologic conditions associated with chronic inflammation. These cells are characterized by the presence of Gr1 and CD11b markers on their surfaces. Gr1+CD11b+ cells isolated from aged mice possess an ability to suppress T cell proliferation/activation and produce heightened levels of proinflammatory cytokines, both constitutively and upon activation, including IL-12, which promotes an excessive production of IFN-γ. IFN-γ priming is essential for excessive proinflammatory cytokine production and the suppressive activities by Gr1+CD11b+ cells from aged mice. These cells suppress T cell proliferation through an NO-dependent mechanism, as depletion of splenic Gr1+ cells reduces NO levels and restores T cell proliferation. Insights into mechanisms responsible for the proinflammatory and immune suppressive activities of Gr1+CD11b+ cells from aged mice have uncovered a defective PI3K–Akt signaling pathway, leading to a reduced Akt-dependent inactivation of GSK3β. Our data demonstrate that abnormal activities of the Gr1+CD11b+ myeloid cell population from aged mice could play a significant role in the mechanisms responsible for immune senescence.

No abstract

About 80% of the consumers worldwide use herbal medicine (HMs) or other natural products. The percentage may vary significantly (7%-55%) among pregnant women, depending upon social status, ethnicity, and cultural traditions. This manuscript discusses the most common HMs used by pregnant women, and the potential interactions of HMs with conventional drugs in some medical conditions that occur during pregnancy (e.g., hypertension, asthma, epilepsy). It also includes an examination of the characteristics of pregnant HM consumers, the primary conditions for which HMs are taken, and a discussion related to the potential toxicity of HMs taken during pregnancy. Many cultures have used HMs in pregnancy to improve wellbeing of the mother and/or baby, or to help decrease nausea and vomiting, treat infection, ease gastrointestinal problems, prepare for labor, induce labor, or ease labor pains. One of the reasons why pregnant women use HMs is an assumption that HMs are safer than conventional medicine. However, for pregnant women with pre-existing conditions like epilepsy and asthma, supplementation of conventional treatment with HMs may further complicate their care. The use of HMs is frequently not reported to healthcare professionals. Providers are often not questioning HM use, despite little being known about the HM safety and HM-drug interactions during pregnancy. This lack of knowledge on potential toxicity and the ability to interact with conventional treatments may impact both mother and fetus. There is a need for education of women and their healthcare professionals to move away from the idea of HMs not being harmful. Healthcare professionals need to question women on whether they use any HMs or natural products during pregnancy, especially when conventional treatment is less efficient and/or adverse events have occurred as herbaldrug interactions could be the reason for these observations. Additionally, more preclinical and clinical studies are needed to evaluate HM efficacy and toxicity.