Increased lytic efficiency of bovine macrophages trained with killed mycobacteria

Innate immunity is evolutionarily conserved in multicellular organisms and was considered to lack memory until very recently. One of its more characteristic mechanisms is phagocytosis, the ability of cells to engulf, process and eventually destroy any injuring agent. We report the results of an ex vivo experiment in bovine macrophages in which improved clearance of Mycobacterium bovis (M. bovis) was induced by pre-exposure to a heat killed M. bovis preparation. The effects were independent of humoral and cellular adaptive immune responses and lasted up to six months. Specifically, our results demonstrate the existence of a training effect in the lytic phase of phagocytosis that can be activated by killed mycobacteria, thus suggesting a new mechanism of vaccine protection. These findings are compatible with the recently proposed concept of trained immunity, which was developed to explain the observation that innate immune responses provide unspecific protection against pathogens including other than those that originally triggered the immune response.Funding for these studies was provided by the EU project WildTBVac (Contract #613799) and by grants from the Instituto Nacional de Investigación y Tecnología Agraria y alimentaria (INIA, RTA2011-00049) and the Ministry of Science (MINECO, AGL2014-56305) and European Funds Regional Development (FEDER).Peer Reviewe

Viral ADP-ribosyltransferases attach RNA chains to host proteins

The mechanisms by which viruses hijack their host’s genetic machinery are of enormous current interest. One mechanism is adenosine diphosphate (ADP) ribosylation, where ADP-ribosyltransferases (ARTs) transfer an ADP-ribose fragment from the ubiquitous coenzyme nicotinamide adenine dinucleotide (NAD) to acceptor proteins 1. When bacteriophage T4 infects Escherichia coli, three different ARTs reprogram the host’s transcriptional and translational apparatus 2,3. Recently, NAD was identified as a 5′-modification of cellular RNA molecules in bacteria and higher organisms 4-6. Here, we report that bacteriophage T4 ARTs accept not only NAD, but also NAD-RNA as substrate, thereby covalently linking entire RNA chains to acceptor proteins in an “RNAylation” reaction. One of these ARTs, ModB, efficiently RNAylates its host protein target, ribosomal protein S1, at arginine residues and strongly prefers NAD-RNA over NAD. Mutation of a single arginine at position 139 abolishes ADP-ribosylation and RNAylation. Overexpression of mammalian ADP-ribosylarginine hydrolase 1 (ARH1), which cleaves arginine-phosphoribose bonds, shows a decelerated lysis of E. coli when infected with T4. Our findings not only challenge the established views of the phage replication cycle, but also reveal a distinct biological role of NAD-RNA, namely activation of the RNA for enzymatic transfer. Our work exemplifies the first direct connection between RNA modification and post-translational protein modification. As ARTs play important roles in different viral infections, as well as in antiviral defence by the host 7, RNAylation may have far-reaching implications.Competing Interest StatementThe authors have declared no competing interest

Evidence of a characteristic ignition length of a flame

Ignition process of vegetation from a cylindrical flame radiation is examined using Koo and Pagni [1] model. The radiation flux is power-law decreasing with distance [2], while the ignition time increases exponentially. This last behavior yields a characteristic length of fuel ignition from a flame, inducing a percolation type phase transition

Role of weighting and long-range connections on the dynamics of front propagation

Percolation and non-equilibrium front propagation in a two-dimensional network modeling wildfire spread is studied. The model includes two long-range interactions; a deterministic and a probabilistic one induced by firebrand emission. It includes also a time weighting process. Three weight-dependent regimes were found previously; dynamical, static, and non-propagative regime [12]. In the absence of probabilistic interaction, the percolation threshold dependence on the weight does not depend on the deterministic interaction. The dynamical regime is found to belong to the dynamical percolation universality class and the static regime to the random deposition class. In the presence of probabilistic interactions, a minimum percolation threshold is found due to the scaling effects. The dynamical exponents belong to a new universality class