SOME CHARACTERISTICS OF THE ORAL CAVITY AND TEETH OF COSMONAUTS ON MISSIONS TO THE INTERNATIONAL SPACE STATION.

Earlier studies were furthered by examination of parodentium anaerobic microbiota and investigation of gingival liquid immunological factors in space flight. Immunoglobulins were measured using the .enzyme immunoassay (EM). The qualitative content of keya parodentium pathogens is determined with state-of-the-art molecular biology technologies such as the polymerase chain reaction. Statistical data processing was performed using the principle component analysis and ensuing standard statistical analysis. Thereupon, recommendations on cosmonaut's oral and dental hygiene during space mission were developed.

Gender- and menstrual phase dependent regulation of inflammatory gene expression in response to aerobic exercise.

The immunological reaction to exercise has been investigated with increasing intensity in the last 10-20 years, with most human studies performed in male subjects. Recently, gender-specific aspects have received growing attention, but studies carefully monitoring the influence of gender including the menstrual cycle, are rare. Here, we report gene expression patterns in response to a run at 93% of the individual anaerobic threshold of 9 women with regular menstrual cycles and no use of oral contraceptives who ran both at day 10 (follicular phase, F) and at day 25 (luteal phase, L) of their cycle. 12 male subjects (M) served as controls. The mRNA was pooled group wise and processed on a gene expression microarray encompassing 789 genes, including major genes of the inflammatory and anti-inflammatory reaction. The differences of gene expression between time points to (before run) and t1 (after run) were analyzed. Females in L showed a higher extent of regulation than females in F or men. Among those genes which were up-regulated above 1.5 fold change (log2) pro-inflammatory genes were significantly enriched (p = 0.033, after Bonferroni correction) in L, while this was not the case in F or M. Conversely, women in L showed a strong trend towards downregulation of anti-inflammatory genes. Some prominent genes like IL6 (coding for interleukin-6), and IL1RN (also termed IL1RA, coding for interleukin-1 receptor antagonist) were clearly regulated in opposite directions in L as opposed to F and M. In conclusion, women in L showed a distinctly different pattern of gene regulation in response to exercise, compared with women in F or M. The overall direction of gene expression changes of women in L is clearly pro-inflammatory. This finding accentuates a need for careful consideration of the female cyclic phase when investigating women in exercise immunology studies. Our results may also have implications relevant to other forms of stress in females.

Metabolic reprogramming towards aerobic glycolysis correlates with greater proliferative ability and resistance to metabolic inhibition in CD8 versus CD4 T cells.

T lymphocytes (T cells) undergo metabolic reprogramming after activation to provide energy and biosynthetic materials for growth, proliferation and differentiation. Distinct T cell subsets, however, adopt metabolic programs specific to support their needs. As CD4 T cells coordinate adaptive immune responses while CD8 T cells become cytotoxic effectors, we compared activation-induced proliferation and metabolic reprogramming of these subsets. Resting CD4 and CD8 T cells were metabolically similar and used a predominantly oxidative metabolism. Following activation CD8 T cells proliferated more rapidly. Stimulation led both CD4 and CD8 T cells to sharply increase glucose metabolism and adopt aerobic glycolysis as a primary metabolic program. Activated CD4 T cells, however, remained more oxidative and had greater maximal respiratory capacity than activated CD8 T cells. CD4 T cells were also associated with greater levels of ROS and increased mitochondrial content, irrespective of the activation context. CD8 cells were better able, however, to oxidize glutamine as an alternative fuel source. The more glycolytic metabolism of activated CD8 T cells correlated with increased capacity for growth and proliferation, along with reduced sensitivity of cell growth to metabolic inhibition. These specific metabolic programs may promote greater growth and proliferation of CD8 T cells and enhance survival in diverse nutrient conditions.

mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity.

Epigenetic reprogramming of myeloid cells, also known as trained immunity, confers nonspecific protection from secondary infections. Using histone modification profiles of human monocytes trained with the Candida albicans cell wall constituent ß-glucan, together with a genome-wide transcriptome, we identified the induced expression of genes involved in glucose metabolism. Trained monocytes display high glucose consumption, high lactate production, and a high ratio of nicotinamide adenine dinucleotide (NAD(+)) to its reduced form (NADH), reflecting a shift in metabolism with an increase in glycolysis dependent on the activation of mammalian target of rapamycin (mTOR) through a dectin-1-Akt-HIF-1α (hypoxia-inducible factor-1α) pathway. Inhibition of Akt, mTOR, or HIF-1α blocked monocyte induction of trained immunity, whereas the adenosine monophosphate-activated protein kinase activator metformin inhibited the innate immune response to fungal infection. Mice with a myeloid cell-specific defect in HIF-1α were unable to mount trained immunity against bacterial sepsis. Our results indicate that induction of aerobic glycolysis through an Akt-mTOR-HIF-1α pathway represents the metabolic basis of trained immunity.

Comment on "Some immunomodulatory effects of probiotic bacteria might be due to porcine neutrophil elastase inhibitor, a serpin present in MRS broth" [Immunol. Lett. (December) (in press) 1].

Serpins that are present in MRS broth were suspected to be responsible for some of the observed immunomodulatory effects of probiotic bacteria conditioned media. Some comments on this reporting, together with considerations dealing with manipulation of spent culture media and possible interfering effects, are discussed.

Some immunomodulatory effects of probiotic bacteria might be due to porcine neutrophil elastase inhibitor, a serpin present in MRS broth.

Use of conditioned media (CM) is a common practice for the study of the immunomodulatory effects of probiotic bacteria on the human host. Serpins and other immunomodulatory proteins/peptides that are present in CM may be responsible for some of the observed effects, which in fact might have been attributed to probiotic bacteria. The exact effects of serpin have thus to be assessed.

Synergistic effect of hyperoxia and immunoglobulin A on mucosal barrier defense.

BACKGROUND: Hyperoxia has been reported to be protective against gut-derived sepsis. Although secretory immunoglobulin A (IgA) is primarily responsible for humoral defense of mucosal surfaces, a potential synergistic effect with hyperoxia is unknown. An asanguineous cell monolayer system was used to study these aspects in vitro. METHODS: MDCK cells were grown as polarized monolayers in a two-chamber culture system. Apical chambers were inoculated with 10(8) Escherichia coli M14 with or without polyclonal IgA and incubated in a 21 or 95% O2 environment. Basal medium was sampled at 90 and 180 minutes for bacterial translocation. In a second experiment, MDCK cells were lysed at 90 minutes and intracellular bacteria were quantitated. RESULTS: Bacterial translocation was decreased versus normoxia by the treatment groups IgA without hyperoxia or IgA with hyperoxia at 90 minutes. Bacterial internalization at 90 minutes was reduced to the greatest extent by the combined effects of hyperoxia and IgA. Translocation data at 180 minutes confirmed the additional protective effect of hyperoxia with IgA. CONCLUSION: Hyperoxia exerts a significant protective effect on barrier function independent of enhanced leukocyte function. Hyperoxia has an added effect to the mucosal defense provided by IgA.