Recognition of S100 proteins by signal inhibitory receptor on leukocytes-1 negatively regulates human neutrophils

Signal inhibitory receptor on leukocytes-1 (SIRL-1) is an inhibitory receptor with a hitherto unknown ligand, and is expressed on human monocytes and neutrophils. SIRL-1 inhibits myeloid effector functions such as reactive oxygen species (ROS) production. In this study, we identify S100 proteins as SIRL-1 ligands. S100 proteins are composed of two calcium-binding domains. Various S100 proteins are damage-associated molecular patterns (DAMPs) released from damaged cells, after which they initiate inflammation by ligating activating receptors on immune cells. We now show that the inhibitory SIRL-1 recognizes individual calcium-binding domains of all tested S100 proteins. Blocking SIRL-1 on human neutrophils enhanced S100 protein S100A6-induced ROS production, showing that S100A6 suppresses neutrophil ROS production via SIRL-1. Taken together, SIRL-1 is an inhibitory receptor recognizing the S100 protein family of DAMPs. This may help limit tissue damage induced by activated neutrophils.Chemical Immunolog

Immune inhibitory receptors in host–microbe interaction

The immune system protects the organism from disease, but inappropriate immune responses can also damage it. Inhibitory receptors can dampen immune responses and prevent tissue damage and inflammatory diseases. In the human genome, genes for over 300 potential immune inhibitory receptors are present. Here, we explore the possible roles inhibitory receptors play in regulating immune responses, in particular the response to bacteria. We suggest two different groups of inhibitory receptors with separate functions and use mathematical models to illustrate their possible modes of operation. We further identify the human S100 family of proteins as the first known ligands for the inhibitory receptor Signal inhibitory receptor on leukocytes-1 (SIRL-1). S100 proteins are released from damaged cells, and we show that SIRL-1 recognises several S100 proteins, suppressing neutrophil ROS production. We suggest that SIRL-1 activation by S100 proteins may help limit tissue damage caused by the immune response. We also show that a group of bacterial peptides, the staphylococcal phenol-soluble modulins, and the structurally and functionally related human peptide cathelicidin LL-37, activate SIRL-1. This suggests that α-helical peptides with an amphipathic arrangement of hydrophobicity may represent a potential molecular pattern recognised by SIRL-1. Furthermore, we argue that also other inhibitory receptors recognise endogenous and microbial patterns. We propose that these inhibitory pattern recognition receptors provide context and help mediate tolerance to microbes and balance responses to danger signals The insights gained here will guide future directions for using SIRL-1 and other inhibitory receptors as therapeutic targets

Production of apples pursuant to the production system \u27\u270,0 residue\u27\u27

V letu 2009 so bili narejeni štirje poizkusi na lokacijah in sortah: Sadjarstvo Mirosan s sorto Elstar, UKC Pohorski dvor s sorto Jonagold, Sadjarstvo Blanca s sorto Idared in Sadjarski center Gačnik s sorto Zlati delišes. Primerjali smo integrirano pridelavo in \u27\u270,0 residue\u27\u27 pridelovalni sistem. Prvo smo škropili po načelih IPS. Drugo pa prvo polovico rastne dobe po načelih IPS, od julija naprej pa z biotičnimi pripravki. Vsi ostali tehnološki ukrepi so pri obeh sistemih enaki. Rezultati kažejo, da so ostanki pesticidov v sadju pri \u27\u270,0 residue\u27\u27 pridelovalnem sistemu najmanjši pri sorti \u27Jonagold\u27 (10 aktivnih snovi pod mejo detekcije). Največ ostankov v \u27\u270,0 residue\u27\u27 pridelovalnem sistemu je bilo pri sorti \u27Idared\u27 (samo trije pripravki pod mejo detekcije). V primerjavi z integrirano pridelavo so pridelki manjši za 2-8 %. Najmanjši delež pridelka I. razreda je bil pri \u27Idaredu\u27 (55 %), največji pa pri \u27Jonogoldu\u27 (82 %) v sistemu \u27\u270,0 residue\u27\u27 in v IPS največji pri \u27Jonagoldu\u27 (87 %) in najmanjši pri \u27Zlatem delišesu\u27 (65 %).In the year 2009 four tests have been executed on the following locations and cultivars: Sadjarstvo Mirosan with the cultivar Elstar, UKC Pohorski dvor with the cultivar Jonagold, Sadjarstvo Blanca with the cultivar Idared and Sadjarski center Gačnik with the cultivar Golden Delicious. We have compared integrated production and the \u27\u270,0 residue\u27\u27 production system. The first were sprayed by IPS principles. The others were sprayed for the first half of the growing period by IPS principles and from July on with biotic preparations. All other technological measures are the same with both systems. The results show, that there are the lowest pesticide residues in fruit of the cultivar Jonagold from \u27\u270,0 residue\u27\u27 production systems (10 active substances below detection limit). Most residues from \u27\u270,0 residue\u27\u27 production systems were found in the cultivar Idared (only three preparations below detection limit). Compared to integrated production, the produce is smaller by 2-8 %. The smallest portion of first class produce was with Idared (55 %), and the biggest with Jonagold (82 %) from the \u27\u270,0 residue\u27\u27 system and from IPS the biggest with Jonagold (87 %) and smallest with Golden Delicious (65 %)

Effect of fertilization with nitrogen and sulphur on yield and quality of garlic (Allium sativum L. ) variety \u27Gardos \u27

Poskus smo izvedli za namenom, da bi ugotovili, kako na količino in kakovost pridelka česna, vplivata gnojenje z žveplom in eno ali dvakratno dognojevanje z dušikom. Novembra 2013 smo na Laboratorijskem polju Biotehniške fakultete v Ljubljani zasnovali poskus v 4 ponovitvah. V poskus smo vključili gnojenje z žveplom (negnojeno (S0), gnojeno s 50 kg S/ha (S50) in 100 kg S/ha (S100)) in dognojevanje z dušikom (negnojeno (N0), 1x dognojeno (N80) in 2x dognojeno (N50+30)). Imeli smo 9 obravnavanj (S0N0, S0N80S0N50+30S50N0S50N80S50N50+30S100N0, S100N80 in S100N50+30), ki smo jih naključno porazdelili znotraj ene ponovitve. Za naš poizkus smo izbrali špansko sorto česna \u27Gardos\u27. Gnojenje z žveplom ni imelo značilnega vpliva na pridelek česna, medtem ko je gnojenje z dušikom značilno povečalo pridelek (14,2 ± 1,80 t/ha pri N80 in 12,9 ± 0,7 t/ha pri N50+30) glede na negnojene rastline (8,20± 0,6 t/ha pri N0). Eno ali dvakratno dognojevanje z dušikom na količino pridelka in kakovost čebulic česna ni imelo značilnega vpliva. Gnojenje z žveplom in dušikom ni imelo značilnega vpliva na delež osušitve pridelka česna. Najbolj (30±4 %) se je osušil pridelek česna z obravnavanja S100N80, najmanj (21±6 %) z obravnavanja S50N80. Gnojenje z dušikom je značilno povečalo maso in premer čebulice, število strokov v čebulici in maso posameznega stroka glede na negnojene rastline. Gnojenje z žveplom na morfološke lastnosti čebulic ni imelo značilnega vpliva.The aim of our study was to evaluate the impact of nitrogen and sulphur fertilization on the yield and quality of garlic bulbs. In the experiment, which was conducted from November 2013 till July 2014, on the Experimental field of the Biotechnical Faculty in Ljubljana in 4 repetitions, different fertilization treatments with nitrogen (N) and sulphur (S) were performed: fertilization with 50 kg S/ha (S50) and 100 kg S/ha (S100) and without sulphur (S0)fertilization with 80 kg N/ha at one application N (80) and at two applications (N50+30) and without N (N0), and their combinations. Together we had 9 treatments, which were randomly assigned to each repetition. The Spanish garlic cultivar \u27Gardos\u27 was included in the experiment. Fertilization with sulphur did not affect significantly the yield of garlic bulbs, while nitrogen fertilization significantly increased the yield (14.2± 1.8 t/ha at N80 and 12.9± 0.7 t/ha at N50+30) regarding to the unfertilized plants (8.20± 0.6 t/ha). The way of nitrogen application (once or twice) did not significantly influence the yield and quality of garlic bulbs, neither the percentage of the weight loss of garlic bulbs. After one week drying on the sun, the highest percentage of weight loss was 30±4 % at plants from treatment S100N80 and the lowest (21±6 %) was at treatment S50N80. The nitrogen fertilization significantly increased the mass and diameter of garlic bulbs, the number of cloves per bulb and the mass of individual clove in comparison to the unfertilized plants

Signal inhibitory receptor on leukocytes-1 recognizes bacterial and endogenous amphipathic alpha-helical peptides

Signal inhibitory receptor on leukocytes-1 (SIRL-1) is a negative regulator of myeloid cell function and dampens antimicrobial responses. We here show that different species of the genus Staphylococcus secrete SIRL-1-engaging factors. By screening a library of single-gene transposon mutants in Staphylococcus aureus, we identified these factors as phenol-soluble modulins (PSMs). PSMs are amphipathic alpha-helical peptides involved in multiple aspects of staphylococcal virulence and physiology. They are cytotoxic and activate the chemotactic formyl peptide receptor 2 (FPR2) on immune cells. Human cathelicidin LL-37 is also an amphipathic alpha-helical peptide with antimicrobial and chemotactic activities, structurally and functionally similar to alpha-type PSMs. We demonstrate that alpha-type PSMs from multiple staphylococcal species as well as human cathelicidin LL-37 activate SIRL-1, suggesting that SIRL-1 recognizes alpha-helical peptides with an amphipathic arrangement of hydrophobicity, although we were not able to show direct binding to SIRL-1. Upon rational peptide design, we identified artificial peptides in which the capacity to ligate SIRL-1 is segregated from cytotoxic and FPR2-activating properties, allowing specific engagement of SIRL-1. In conclusion, we propose staphylococcal PSMs and human LL-37 as a potential new class of natural ligands for SIRL-1.Chemical Immunolog