SIICA-DGfI 2011 Joint Meeting: Front-line immunology with sensorial stimulations, neuromuscular activity and phago/pinocytosis

Authors


Introduction

At the end of September 2011, SIICA and DGfI, i.e. the Italian and German Societies for Immunology respectively, put together their forces and organized a joint meeting at the PalaRiccione Congress Hall in Riccione, a splendid Italian town on the Adriatic coast. The meeting was attended by a total of 950 scientists who came not only from the countries of the two organizing Societies, but also from different parts of the world, including Japan, Iran, Austria, Spain, Switzerland, UK and USA. The organizing Committee was smart enough to book four wonderful sunny days for the conference, a prerequisite for some of the planned activities.

The SIICA-DGfI Meeting was preceded by the EFIS/EJI course on “Basic and Translational Immunology: The Innate Immunity” (http://www.immunology2011.it/satelliteevents.asp and 1), with 11 lectures on ”Soluble mediators of the innate immunity” and “Cells of the innate immunity and their receptors”. This part of the meeting was attended by 60 young scientists.

The main meeting (http://www.immunology2011.it) was structured into three keynote lectures, 12 parallel symposia, 14 parallel workshops, 14 poster sessions, 1 IFIACI-DGAKI satellite symposium on “Mechanisms of chronic inflammation and allergic immune response” and two clinical satellite meetings, the first with the Italian Society of Rheumatology and the second with the Italian Society for Infectious and Tropical Diseases. There were 635 accepted abstracts, and a total of 145 oral presentations. In addition to all this immunology, the meeting had a vibrant social program (as discussed below). The registration fee of the main conference was kept affordably low, taking into account the difficult economic situation in which all of us currently live and the cuts that have hit the research community in recent years. Fortunately, the meeting received crucial support from 7 silver and 17 bronze sponsors (http://www.immunology2011.it/sponsor.asp), 7 minor sponsors, 6 pharmaceutical companies for the clinical symposia and the cooperation of 2 media operations, including the European Journal of Immunology.

The first moments: Dual stimulation of the visual and the auditory cortex

As a teaser, just before the opening ceremony, the opening symposium entertained the fascinating new developments in microscopy that allow cells of the immune system to be tracked in vivo, capturing the dynamics of cellular movements and interactions. While M. Gunzer (Magdeburg/Essen) observed neutrophils at work, M. Iannacone (Milano) followed lymphocytes in a viral infection. How microscopy can be used to identify and track individual molecules was discussed by M. Reth (Freiburg), who provided evidence for an oligomeric resting state of the B-cell antigen receptor and the perturbation of this state by activation.

The opening ceremony started with the two national anthems followed by a concert given by a duo from Modena: the Butterflies. Francesca Bergamini, vocals, and Alessandra Fogliani at the piano, performed songs in German, Italian, Spanish and English (Fig. 1). The first keynote lecture of the meeting was sponsored by EFIS and given by Prof. Klaus Rajewsky (Boston, USA). He presented his in-depth analysis of B-cell activation and the role of c-myc and IKK in the pathogenic transformation for the survival and expansion of lymphoma cells. At the end of the opening ceremony, the President of the DGfI, Prof. Dieter Kabelitz (Kiel), awarded Prof. Hans-Hartmut Peter (Freiburg) honorary membership of the DGfI for his extraordinary impact on clinical immunology and rheumatology, and his contributions to the understanding of immunodeficiencies.

Figure 1.

“Mackie Messer (Mack the knife)” by Bertold Brecht and Kurt Weill, interpreted by Francesca Bergamini (voice) and Alessandra Fogliani (piano), dedicated to all those interested in killer cells.

After the opening session, high up on the PalaRiccione terrace with its impressive view of the sea bathed in a beautifully colored sunshine, a famous brass band from Münster (the NorthWestBrass, led by Kapellmeister Roland Göhde, Fig. 2) had the opportunity to present a new poly-functional program – from J. S. Bach to Bob Dylan, passing through Gershwin, Henry Mancini, The Beatles, Abba – to more than 600 persons who were also interested in testing the speed of evaporation of 350 bottles of ice-cold Prosecco (from Travani A. et al., Arzene, Italy, a total of 262.50 L) and 6 bottles of water of unknown origin (a total of 9.50 L, p<0.00001 versus Prosecco, by ANOVA). Furthermore, participants could thoroughly analyze, in a non-blind manner, three independent but very big pieces of 50.00 kg pork-shaped “mortadella” (that some erroneously still call “Bologna”, and was kindly provided by SIICA member Luca Cicchetti), a total of 150.00 kg, compared with 48.00 kg of 24-month-old home-made original parmesan (p<0.001 versus mortadella), and an adequate, but impossible to calculate, amount of “focaccia” and “piadina” (i.e. type of breads you can find only in the Romagna region).

Figure 2.

The “NorthWestBrass” quintet in action, with Norbert Fabritius (trumpet), Georg Potthoff (trumpet), Roland Göhde (French horn), Thomas Brand (trombone), Stephan Schulze (tuba).

The second day: From immunology

The second day of the meeting saw a strong scientific program dealing with topics related to NK cells and innate immunity, immunodeficiencies, immunoregulation, mucosal immunity and veterinary immunology. The role of radical oxygen species (ROS)-generation in the up-regulation of NKG2D and DNAM-1 expression was reported by A. Santoni (Rome), while C. Watzl (Heidelberg) showed that CD107a, a protein present on the inner leaf of cytotoxic granules, protects NK cells from degranulation-associated damage. C. Romagnani (Berlin) dissected NK-cell differentiation stages according to the CD62L and other markers and showed that studying NK-cell clustering by principal component analysis enables immature and mature NK cells to be tracked in vivo after NK-cell adoptive transfer and hematopoietic stem cell transplantation. The role of the CX3CR1/CX3CL1 axis was studied by G. Bernardini (Rome) in a modified mouse model in which the CX3CR1 gene was replaced by GFP, showing that CX3CR1 regulates NK-cell accumulation in the bone marrow, likely by affecting NK-cell differentiation into KLRG1+ cells. J. D. Haas (Hannover) studied the ontogeny of IL-17-producing γδ T cells, and found that IL-17 was not generated after the induction of Rag-1 in an inducible Rag-1 KO mouse model. However, the generation of γδ T17 cells could be restored by thymus transplantation in adult animals.

C. Agostini (Padova) reported on the role of common variable immunodeficiency (CVI) in provoking damage in the lung. CVI was also investigated by M. Lima Gomes Ochtrop (Freiburg), who described a number of abnormalities among bone marrow-resident T and B cells, such as the presence of diffuse and nodular CD3+ infiltrates, or a partial block in B-cell development at the B-I to pre-B-II cell stage. H. Eibel (Freiburg) had screened a large cohort of patients that suffer from primary antibody deficiency and found that two of them had a homozygous deletion in the BAFF-R gene causing a severe block of B-cell development at the stage of transitional B cells.

O. Pabst (Hannover) demonstrated that oral tolerance requires the sequential interaction of T cells with different populations of APCs in the mesenteric lymph nodes and thereafter in the intestinal lamina propria. The unexpected role of the anti-coagulative protein C (PC) in controlling the integrity of the epithelial barrier and intestinal inflammation was described by S. Vetrano (Rozzano) who had studied colonic sections from patients suffering from inflammatory bowel disease. S. Vetrano had also generated PC–/– transgenic mice, which were found to develop spontaneous intestinal inflammation and severe colitis, along with decreased expression of JAM-A, claudin-3 and alterations in ZO-1 expression.

A joint session held in collaboration with the Italian Society for Rheumatology hosted different talks. The effects TNF-α-blocking agents on monocytes and T cells in rheumatoid arthritis (U. Wagner, Leipzig), the role of biological drugs in the treatment of ANCA-associated systemic vasculitis (R. A. Sinico, Milan), as well as novel pathways and possible new targets in SLE (F. R. Spinelli, Rome), were all discussed.

In the afternoon, talks were given by M. Cassatella (Verona) who reviewed the ability of neutrophils to undertake bidirectional cross talks with different cell types, including DCs, NK, iNKT and also unpolarized T cells. T. Laskay (Lübeck) showed that intracellular pathogens can globally diminish the expression of IFN-γ-regulated genes. The development of the thymus during evolution and, in particular, its phylogenetic pendant in jawless vertebrates (agnathans) was discussed by T. Boehm (Freiburg), while L. Screpanti (Rome) presented data on the relative contributions and interconnectivity of Notch3, the pre-TCR and NF-kB in the development of T cells. A. Diefenbach (Freiburg) reported that dietary AhR ligands dynamically regulated postnatal development of lymphoid follicles by controlling the pool size of LTI-like ILCs. Concerning tumor immunology, T. Blankenstein (Berlin) reported an aberrant rather than protective T-cell response, resulting in tolerance at the premalignant stage, while P. Yu (Marburg) showed that TLR-3, -7 and -9 can protect against murine T-cell lymphomas caused by endogenous retroviruses. The role of protein kinase CK2 as a pro-survival molecule that protects multiple myeloma cells from bortezomib, the first therapeutic proteasome inhibitor, was discussed by F. Cinetto (Padova).

In the late afternoon, after viewing and discussing more than 300 posters and attending several workshops, members participated in the Assembly of their respective Society, both meetings being characterized by a very relaxed atmosphere (p<0.000001 versus several other assemblies that we have attended). The new SIICA board with Prof. V. Barnaba (Rome) as the new President was elected during the SIICA Assembly.

…. to the induction of stress molecules in muscles of different nationalities

Finally, one of the most exciting moments of the meeting arrived. If you put together any number of randomly selected Italians and Germans aged 4 years or older, you can be sure that after a couple of nanoseconds a challenging discussion starts about who are, or who were, the best football (or soccer, for readers in the new world) players, trainers, or national teams. Over the last few decades, very elegantly and in a politically correct manner, Germany won the world football Championship in Italy (in 1990) and Italy won the tournament in Germany (in 2006). A football match of Italian versus German immunologists was thus unavoidable. With the precious help of Ms. Annanora Vanni, the perfect organizer and leader of “Riccione Congressi”, and the participation of the Vice-Major of the city for the official kick-off, 44 outbred male immunologists of both countries and one heroic German female (p<0.00001, by squared Chi test) met for a beach soccer challenge at night (Fig. 3A–F).

Figure 3.

Football match of Italian versus German Immunologists. (A) The “Best Player” Committee discusses in front of the DGfI booth the criteria for selecting the player. (B–D) The two teams (and the referee) before the beginning of the match. Note the happy faces and intact legs. White shirts: Germans, blue shirts: Italians; E–F) Players in action.

Needless to say, finding a suitable referee was an issue, and heavily debated until the two captains (the authors of this report) finally agreed on Josè Enrique O'Connor Blasco, a Spanish fellow scientist from the University of Valencia, who was expected to lecture on “Cytomics and Immunology” the next day. At the end of the match, all players and the audience were impressed by him, and were very respectful even when he denied a couple of penalties – to both teams.

As for the precise chronicle of the match – the first part of the first half was characterized by the physical and athletic dominance of the Germans, who scored two goals within a few minutes. But then the Italians were able to go even. In the second half of the match, Germany scored another two goals, but then Italy went even just two minutes before the end, for a final result of 4-4, that was absolutely perfect, mainly because the organizers had bought only gold medals, and the victory of one team would have been a problem. To conclude this epic story, the title of best player was shared by Lorenzo Cosmi (Florence) and Benjamin Weisst (Berlin).

Third day: From complement, miRNA, vaccines, B cells…

The third day of science started with symposia on complement and soluble mediators, microRNAs (miRNAs), vaccines and infections, transplantation and tolerance and B cells. M. Kirschfink (Heidelberg) discussed the main mechanisms by which tumor cells acquire resistance to complement, and F. Tedesco (Trieste) reported on the non-canonical functions of C1q that can be secreted by trophoblasts in order to adhere and partially replace decidual endothelial cells.

The session on miRNAs was attended by a huge crowd. The miRNome of different human lymphocyte subsets was discussed by S. Abrignani (Milan), in particular the specific naïve CD4+ T-cell miRNA signature that inhibits GRB2, LNK, IFN-γ, IL-2Rβ, IL-10Rα and Blimp1. miRNA-regulated gene expression in chronically activated effector memory Th cells was studied by M.-F. Mashreghi (Berlin) who described the regulation of clonal expansion of activated T cells by miR-182. miRNA-182, which is induced after activation of naïve T cells and regulated by IL-2/Stat5, downregulates the antiproliferative transcription factor Foxo1, which results in chronic T-cell proliferation. Another miRNA is specifically induced in chronically activated effector/memory Th1 cells, controlling survival of these cells by targeting Bim and Pten. G. Curtale (Milan) described a novel class of anti-inflammatory miRNAs that modulate TLR4-signaling pathways at multiple steps. Examples are the miRNA cluster 99b/125a-5p/let7e, miR-187 and miR-146b, which are induced by LPS in an IL-10-dependent manner, while miR-511 is induced by dexamethasone. M. Pagani (Milan) presented miRNA profiles in 17 lymphocyte subsets and evidence for the importance of miR-125b in the regulation of genes related to T-cell differentiation (IFNG, IL2RB, IL10RA, PRDM1).

Concerning vaccines and infections, the mechanism of action of MF59, an oil-in-water emulsion adjuvant, was described by E. De Gregorio (Siena). Based on the immune response of immune individuals in endemic areas, K. Matuschewski (Berlin) summarized his findings on the rational development of a whole-organism anti-malaria vaccine, while V. Barnaba (Rome) described the polyclonal CD8+ T-cell response to apoptotic self-antigens related to the chronic evolution of hepatitis C. The multi-level host responses to influenza A virus infection was studied by E. Wilk (Braunschweig) who recorded the transcriptome of the lungs from C57Bl/6J mice over a period of 60 days and presented an extensive description of the transcriptional changes occurring during the switch from innate to acquired immunity.

In the B-cell section, E. Ferretti (Genova) reported that IL-31R is expressed in follicular B lymphoma cells and that its ligand IL-31 triggers tumor cell proliferation, while J. Freitag (Jena) described the attempts and strategies to establish a retrogenic mouse that expresses transgenic anti-HEL membrane IgM receptors.

After the morning symposia and workshops, a keynote lecture focussed on advanced technologies in immunology. E. O'Connor (Valencia) discussed the most recent methods, including the spectacular tool that is mass-spectrometric cytometry, which allows the simultaneous analysis of several dozen of parameters (cell phenotype and functions) in the same cell.

Autoimmunity and chronic inflammation, control of humoral immunity and antigen-presenting cells were some of the topics addressed in the early afternoon. F. Aloisi (Rome) discussed how Epstein Barr virus has gained increased credibility as the main culprit of some major B-cell-related autoimmune diseases (SLE, RA, MS, among others) over recent years. D. Engel (Bonn) discussed how pathogenic Th1 cells are generated in postoperative ileus. The renaissance of transcriptional “Th1” programs was further highlighted by M. Löhning (Berlin) who showed that LCMV infection reprograms Th2 cells into a stable GATA-3+ T-bet+ “Th2+1” hybrid cell subset. Finally, L. Maggi (Florence) provided correlative evidence that “Th1+17” cells play a role in in chronic rheumatic inflammation.

During a symposium on humoral immunity, J. Wienands (Göttingen) identified signal transducers that are involved in the differential activation of IgG memory versus naive IgM B cells. V. T. Chu (Berlin) showed that eosinophils play a critical role in the memory plasma cell survival niche of the bone marrow, and R. Franke (Berlin) highlighted the role of ICOS in cooperation between B and T lymphocytes.

Another focus of the meeting was the regulation of immunity by pathogens and antigen-presenting cells. M. de Bernard (Padova) described that the activation of inflammasomes by the miniferritin TpF1 from Treponema pallidum supports Treg-cell development. By using a model of naive autoantigen-specific T cells, F. Granucci (Milan) showed the complexity of the activating or tolerizing properties of DCs; and the role of kidney DCs in initiating the innate cellular immune response against bacteria causing pyelonephritis was presented by C. Kurts (Bonn). A. Bachem (Berlin) gave further insights into the role of the chemokine receptor XCR1 in CD8+ cross-presentation mouse DCs and in their human homologous, the CD141+ DCs. Finally, A. Cavani (Rome) showed that keratinocytes directly activate plasmacytoid DCs during inflammatory skin diseases.

…to mitochondria required for ATP production and consumption

On the Friday, an important night event, attended by more than 700 scientists, was held in the discotheque Peter Pan, one of the temples of fun at the Adriatic coast, which was completely dedicated to immunology from 9:00 pm to 2:00 am. The first part of the evening was necessary to increase the intracellular energy levels of scientists of all age, and this was not difficult thanks to the excellent food (freshly prepared by the chefs, coordinated by Mr. Giancarlo Pretolani) and the variety of Italian wines offered. As an example, the half-life of two 20 kg cakes, each with the edible logo of one of the Societies, was less than 10 min, including the cutting procedure and the queue (Fig. 4). Then everybody started to dance, and for a few hours molecular and cellular immunologists were not distinguishable anymore.

Figure 4.

Cake ceremony and consequent activation of phagocytosis in the Peter Pan disco.

Last lectures, then everybody goes home

The last day of the conference started with a special session, chaired by E. Sagnelli and organized in collaboration with the Italian Society for Infectious and Tropical Diseases (SIMIT). The immunopathogenesis of HIV, HBV and HCV infections was discussed by M. Clerici (Milan), C. Ferrari (Parma) and M. Mondelli (Pavia), respectively. In parallel, two workshops were held on tumor immunology and antigen presentation. On the occasion of the 30th anniversary of the discovery of AIDS, a special keynote lecture, co-organized with SIMIT, was given by Jay A Levy (San Francisco) who provided a résumé of the past 30 years of HIV history and emphasized the importance of immunology to better comprehend the pathogenesis of the infection, as well as the problems in the development of effective vaccines. A review based on this talk was recently published in this Journal 2. This exciting overview was followed by another keynote lecture, sponsored by EFIS and given by Marco Colonna (St. Louis) who discussed the role of NK-22 innate lymphocytes in mucosal immunity, their functional plasticity and developmental requirements.

The final symposium, dedicated to intracellular immunity, saw lectures by G. Hartmann and S. Wain-Hobson. G. Hartmann (Bonn) discussed how RIG-I mediates immune activation and how RIG-I-RNA ligand interactions activate type I IFN, induce inflammasome activation and pro-apoptotic signaling. S. Wain-Hobson (Paris) discussed the contribution of the APOBECs, a class of cytidine deaminases, in tumorigenesis. A. Gori (Monza) closed the session with a special lecture discussing what infectiologists could learn from immunologists in order to better understand clinical situations of viral infection, paying special attention to HIV.

Concluding remarks

First of all, we apologize to all those scientists who are not quoted in this non-exhaustive report. We were very satisfied with the high quality of the scientific presentations, the interesting discussions, and the number of young scientists who presented their work in Riccione. The linkage “in equilibrium” between an exciting immunological conference and an intense social program created new collaborations and close friendships among the participants of both Societies. Considering that, last but not least, the financial side looks very promising, a similar experiment asks to be repeated.