Selected Articles May 2014
Gut microbiota and blood acute-phase proteins
Influence of the gut microbiota on blood acute-phase proteins
W. Schrödl, B. Kleessen, L. Jäkel, A. A. Shehata and M. Krüger
In this study from the University of Leipzig it is shown that some special bacterial groups of the gastrointestinal tract microbiota have an influence on the concentration of special acute-phase proteins in the blood of cattle.
–This is an indication that special groups of bacteria in the gastrointestinal tract can induce inflammation reactions, says Wieland Schrödl, Veterinary and scientist at the University of Leipzig employed in the Institute of bacteriology and mycology.
A second new finding in this study was the negative acute phase reaction of the C-reactive protein in cattle. In human, dog and pig it is a positive acute phase reactant.
– I was very happy to be able to measure a clear positive correlation between the acute phase protein LBP in blood and the quantity of aerobic gram-negative bacteria and clostridium perfringens in the gastrointestinal tract of cows. On the other side, I have determined a negative correlation between the number of lactobacilli in the gastrointestinal tract and the positive acute phase proteins LBP and haptoglobin. The importance of lactobacilli in the microbiota has been known, but I was able to measure it in this complex system of microbiota and immune system, Wieland Schrödl concludes.
Optimized protocol for generation of specific immunosuppressive human monocyte-derived macrophages
An optimized protocol for human M2 macrophages using M-CSF and IL-4/IL-10/TGF-beta yields a dominant immunosuppressive phenotype
S. Mia, A. Warnecke, X.-M. Zhang and R. A. Harris
In this paper from the Robert Harris group at Karolinska Institutet a panel of polarization protocols for blood derived human monocytes was investigated and compared. The study was undertaken to address how best to induce in vitro an immunosuppressive human macrophage phenotype.
Macrophages are transformed from circulating monocytes into either pro-inflammatory M1 macrophages or immunosuppressive M2 macrophages. The relative balance of M1 cells driving inflammation, and M2 cells regulating the immune response, will determine the final outcome of either chronic inflammation or healing. Manipulation of this M1/M2 balance through adoptive transfer of in vitro pre-activated macrophages is thus a highly interesting therapy. An important aspect will be the stability of the induced anti-inflammatory phenotype.
During the studies of protocols to generate M2 macrophages the group made three major findings:
(a) that a stable, efficiently immunosuppressive M2 phenotype can be induced by specific cytokine stimulation in vitro.
(b) that pre-differentiation with M-CSF prior to M2 induction yields the most efficient final phenotype. This defines the final protocol suggested for use in the clinic.
(c) demonstration that it is possible to induce the immunosuppressive M2 phenotype in monocytes recovered from patients with pro-inflammatory diseases. This indicates proof-of-concept for further use in clinical immunotherapy settings.
Muhammad Sohel Mia, MD, PhD was a PhD student in the group and did recently graduate. He performed the majority of the work included in the paper, and conducted similar phenotypic analyses of mouse macrophages that led to this study of human monocytes.
– When I started working with human monocytes I expected it would be a straightforward approach as I have been working with rodent macrophages before. However, it became obvious at an early stage that human cells do not behave in a similar way to murine cells, and variability between donors was much more extreme than between individual animals. There are number of different methods used in purification of human monocytes and comparing and contrasting the different isolation and purification methods and their effects on human monocytes activation was the most fun part of the project and what lead to this paper.