In vitro response to Candida albicans in cultures of whole human blood from young and aged donors

Invasive infections with opportunistic fungi, such as Candida albicans, have become an increasing problem in aged adults in recent years. This work investigates the influence of human ageing on C. albicans recognition by toll-like receptors (TLRs), essential components of the innate immune system, using a cohort of 96 young (15-42 years) and aged (>70 years) human volunteers. No significant differences between aged and young donors were observed on (1) cell surface TLR2, TLR6 and TLR4 expression on lymphocytes, monocytes and granulocytes, (2) production of cytokines [IL-8, IL-1beta, IL-6, IL-10, tumour necrosis factor (TNF)-alpha and IL-12p70] and prostaglandin E(2) (PGE(2)) by whole human blood in response to C. albicans and (3) fungicidal activity of whole blood. A statistically significant higher titre of natural anti-C. albicans antibodies was found in plasma of volunteers between 80 and 95 years old when compared with other age groups, probably as a consequence of the increased levels of serum Ig that has been described in elderly subjects. Therefore, the results indicate that the increased susceptibility to C. albicans infections in the elderly is not a consequence of defects in TLRs expression or signalling, nor of an impaired fungicidal activity of blood.     

Relationship between interaction sites in the gut, hydrophobicity, mucosal immunomodulating capacities and cell wall protein profiles in indigenous and exogenous bacteria

AIMS: To investigate whether there is a relationship between interaction sites in the gut, hydrophobicity, mucosal immunomodulating capacities and cell wall protein profiles in lactobacilli, bifidobacteria and enterococci. METHODS AND RESULTS: Hydrophobicity, cell wall protein profiles and sites of interaction in the gut (by using fluorescein isothiocyanate-labelled bacteria) were determined for Lactobacillus casei, L. acidophilus, L. fermentum, Bifidobacterium bifidum, B. animalis and Enterococcus faecalis. We also determined the number of immunoglobulin (Ig)A+, tumour necrosis factor (TNF)alpha+, interleukin (IL)-6+ and IL-10+ cells after oral administration of the above bacteria to BALB/c mice. All strains assessed were found to interact with the sites of induction of the immune response in the gut. No correlation with hydrophobicity was observed. When some strains at certain doses were administered to mice, bacterial translocation to liver was observed. The oral administration of indigenous (104 cells day(-1)) and exogenous (107 cells day(-1)) bifidobacteria and lactobacilli for 5 consecutive days activated the systemic and intestinal mucosal immune response in a strain-specific way, independently whether the strain was indigenous or exogenous in relation to the host. The differences in the immunopotentiating capacity of the various strains might be related to the differences in their cell wall protein profiles. CONCLUSIONS: Indigenous bacteria activated the mucosal immune response at a dose significantly smaller than the one required for probiotic exogenous bacteria. However, probiotic exogenous bacteria can be used at high concentrations in fermented dairy products with a great impact on the immune system, favouring its immunomodulation. SIGNIFICANCE AND IMPACT OF THE STUDY: The immunomodulation capacity of probiotic bacteria is strain specific and independent of the specificity of the host. The ability of certain strains to down-regulate the production and release of IL-6 by IL-10 may have potential implications in their use in cases in which cytokine deregulation or excessive production at the mucosal level can be the cause of tissue damage.     

Predictive markers of safety and immunogenicity of adjuvanted vaccines

Vaccination represents one of the greatest public health triumphs; in part due to the effect of adjuvants that have been included in vaccine preparations to boost the immune responses through different mechanisms. Although a variety of novel adjuvants have been under development, only a limited number have been approved by regulatory authorities for human vaccines. This report reflects the conclusions of a group of scientists from academia, regulatory agencies and industry who attended a conference on the current state of the art in the adjuvant field. Held at the U.S. Pharmacopeial Convention (USP) in Rockville, Maryland, USA, from 18 to 19 April 2013 and organized by the International Association for Biologicals (IABS), the conference focused particularly on the future development of effective adjuvants and adjuvanted vaccines and on overcoming major hurdles, such as safety and immunogenicity assessment, as well as regulatory scrutiny. More information on the conference output can be found on the IABS website, http://www.iabs.org/.     

Anthocorid predators learn to associate herbivore-induced plant volatiles with presence or absence of prey

We investigated how the plant‐inhabiting, anthocorid predator, Anthocoris nemoralis, copes with variation in prey, host plant and associated herbivore‐induced plant volatiles and in particular whether the preference for these plant odours is innate or acquired. We found a marked difference between the olfactory response of orchard‐caught predators and that of their first generation reared on flour moth eggs in the laboratory, i.e. under conditions free of herbivory‐induced volatiles. Whereas the orchard‐caught predators preferred odour from psyllid‐infested pear leaves, when offered against clean air in a Y‐tube olfactometer, the laboratory‐reared first generation of (naive) predators did not. The same difference was found when a single component (methyl salicylate) of the herbivore‐induced plant volatiles was offered against clean air. After experiencing methyl salicylate with prey, however, the laboratory‐reared predators showed a pronounced preference for this volatile. This acquired preference did not depend on whether the volatile had been experienced in the juvenile period or in the adult phase, but it did depend on whether it had been offered in presence or absence of prey. In the first case, they were attracted to the plant volatile in subsequent olfactometer experiments, but when the volatile had been offered during a period of prey deprivation, the predators were not attracted. We conclude that associative learning is the most likely mechanism underlying acquired odour preference.     

Bacterial DNA as immune cell activator

Pattern recognition receptors of the innate and adaptive immune systems apparently recognize unmethylated CpG motifs of bacterial DNA. Cells of the innate immune system are activated directly by CpG motifs, and the resulting response dictates a Th1 bias to the developing adaptive immune response. Interestingly, antigen receptor occupancy of cells of the adaptive immune system augments their responsiveness to CpG motifs, suggesting that co-stimulatory mechanisms are operative.     

Formation of immune proteasomes and development of immune system in ontogenesis of mammals

Current concepts of the structure of immune proteasomes and their role in immune response have been considered. The main attention has been paid to the formation of immune proteasomes in secondary lymphoid and nonlymphoid organs during ontogenesis of mammals. The causes of ineffective formation of immune system in early postnatal development have been discussed.