Antimicrobial Immunity Research Articles

Alcohol Abstinence Does Not Fully Reverse Abnormalities of Mucosal-Associated Invariant T Cells in the Blood of Patients With Alcoholic Hepatitis.

OBJECTIVES:Alcoholic hepatitis (AH) develops in approximately 30% of chronic heavy drinkers. The immune system of patients with AH is hyperactivated, yet ineffective against infectious diseases. Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that are highly enriched in liver, mucosa, and peripheral blood and contribute to antimicrobial immunity. We aimed to determine whether MAIT cells were dysregulated in heavy drinkers with and without AH and the effects of alcohol abstinence on MAIT cell recovery.METHODS:MR1 tetramers loaded with a potent MAIT cell ligand 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil were used in multiparameter flow cytometry to analyze peripheral blood MAIT cells in 59 healthy controls (HC), 56 patients with AH, and 45 heavy drinkers without overt liver disease (HDC) at baseline and 6- and 12-month follow-ups. Multiplex immunoassays were used to quantify plasma levels of cytokines related to MAIT cell activation. Kinetic Turbidimetric Limulus Amebocyte Lysate Assay and ELISA were performed to measure circulating levels of 2 surrogate markers for bacterial translocation (lipopolysaccharide and CD14), respectively.RESULTS:At baseline, patients with AH had a significantly lower frequency of MAIT cells than HDC and HC. HDC also had less MAIT cells than HC (median 0.16% in AH, 0.56% in HDC, and 1.25% in HC). Further, the residual MAIT cells in patients with AH expressed higher levels of activation markers (CD69, CD38, and human leukocyte antigen [HLA]-DR), the effector molecule granzyme B, and the immune exhaustion molecule PD-1. Plasma levels of lipopolysaccharide and CD14 and several cytokines related to MAIT cell activation were elevated in patients with AH (interferon [IFN]-α, interleukin [IL]-7, IL-15, IL-17, IL-18, IL-23, IFN-γ, and tumor necrosis factor α). Decreased MAIT cell frequency and upregulated CD38, CD69, and HLA-DR correlated negatively and positively, respectively, with aspartate aminotransferase level. MAIT cell frequency negatively correlated with IL-18. HLA-DR and CD38 levels correlated with several cytokines. At follow-ups, abstinent patients with AH had increased MAIT cell frequency and decreased MAIT cell activation. However, MAIT cell frequency was not fully normalized in patients with AH (median 0.31%).DISCUSSION:We showed that HDC had a reduction of blood MAIT cells despite showing little evidence of immune activation, whereas patients with AH had a severe depletion of blood MAIT cells and the residual cells were highly activated. Alcohol abstinence partially reversed those abnormalities.

Blockade Effects of Anti-Interferon- (IFN-) γ Autoantibodies on IFN-γ-Regulated Antimicrobial Immunity.

The interferon- (IFN-) γ expression is elicited in response to microbial infections and activates immune surveillance by antimicrobial immune elements to induce microbial killing. Patients with adult-onset immunodeficiency who suffer from recurrent infections with microbes, particularly nontuberculous mycobacteria (NTM), commonly display genetic defects in IFN-γ signaling as well as the generation of anti-IFN-γ autoantibodies (autoAbs). Because IFN-γ is an activator of macrophage differentiation and a proinflammatory activator of innate immunity, the blockade effects of the autoAbs present in NTM patient serum on IFN-γ are hypothesized to regulate the antimicrobial function of macrophages. In the presence of patient serum, IFN-γ-induced type 1 macrophage (M1) differentiation was inhibited in PMA-stimulated human monocytic THP-1 cells. Treatment with patient serum significantly blocked the production of proinflammatory factors, including cytokines/chemokines and reactive oxygen/nitrogen species, by M1 macrophages. Importantly, IFN-γ-facilitated phagocytosis and degradation of heat-killed mycobacterium were decreased by cotreatment with patient serum. These results show the blockade activity of anti-IFN-γ autoAbs on IFN-γ-mediated antimicrobial immunity in macrophages.

Nutrient Sensing by the Intestinal Epithelium Orchestrates Mucosal Antimicrobial Defense via Translational Control of Hes1

Metabolic programs and host defense are highly integrated to ensure proper immune responses during stress. Central to these responses, mTOR regulates immune functions by sensing and integrating environmental cues, yet how these systems are coordinated at the intestinal surface remains undefined. We show that the antimicrobial peptide α-defensin is functionally sustained during nutrient deprivation because of regulation of the defensin-processing enzyme MMP7 by microbiota- and host-derived factors. Unlike other antimicrobial peptides, the MMP7-α-defensin axis remains active during nutrient fluctuations, providing essential protection against enteric pathogens. Sustained Mmp7 expression requires themicrobiota and is mediated by de-repression of the transcription activator Atoh1 upon attenuation of the transcriptional repressor Hes1 in intestinal epithelial cells. Hes1 levels are regulated via mTORand controlled translationally, constituting a metabolism-translation-transcription loop. Disrupting this loop by supplying nutrients paradoxically compromises antibacterial defense. Together, these results uncover a regulatory circuit that couples host nutrient status to epithelial antimicrobial immunity.

Study of innate factors in the local immune defense of the genital organs of dogs and cats

Immune system of reproductive organs of animals is represented by a number of cellular and humoral protection factors. Recently, the attention of scientists was attracted by the role of immunocompetent cells, which integrally provide immune homeostasis at all stages of the reproductive function. The purpose of the work was to study the cellular factors of immune defense of mucous membranes of genital organs of dogs and cats. The cytological composition and determination of immunological parameters of vaginal microscope slide were determined by patented methods. Local immunity was determined by the parameters of extracellular protection mechanisms, which consisted in the study of the Oxygen-dependent potential of neutrophil granulocytes (NBT-test) and their ability to form extracellular traps (NETs). Our studies have found that in different stages of the sexual cycle in beach and cats, along with cytological changes in epithelial cells, changes occur in phagocytic protection. In particular, in the post-infusion period there was an increase in the number of intermediate and basal epithelial cells on the surface of which were adhered microorganisms. Along with epithelial cells, activated phagocytes were grouped. Neutrophils showed cytochemical reactivity in the NBT-test, and also formed NETs. At the same time, activated phagocytes absorbed microorganisms, and some epithelial cells formed specific cytoplasmic inclusions, which obviously also has an important role in the antimicrobial immunity of the mucosa. Some neutrophilic granulocytes were in a state of apoptosis. During the sexual cycle in the organism of dogs and cats there are morphology and functional changes in the genital organs, which was accompanied by a change in the cytological picture of vaginal microscope slides. It was established that the antimicrobial protection system plays an important role in the neutrophilic granulocytes, the functional activity of which also has a change. The main mechanisms of extracellular antimicrobial protection of microphages are realized with the involvement of Oxygen species in the excretion system of active forms and the formation of neutrophilic extracellular traps. Epithelial cells are also involved in the formation of immune homeostasis of genital mucous membranes.

Dual actions of group B Streptococcus capsular sialic acid provide resistance to platelet-mediated antimicrobial killing

Circulating platelets have important functions in thrombosis and in modulating immune and inflammatory responses. However, the role of platelets in innate immunity to bacterial infection is largely unexplored. While human platelets rapidly kill Staphylococcus aureus, we found the neonatal pathogen group B Streptococcus (GBS) to be remarkably resistant to platelet killing. GBS possesses a capsule polysaccharide (CPS) with terminal α2,3-linked sialic acid (Sia) residues that mimic a common epitope present on the human cell surface glycocalyx. A GBS mutant deficient in CPS Sia was more efficiently killed by human platelets, thrombin-activated platelet releasate, and synthetic platelet-associated antimicrobial peptides. GBS Sia is known to bind inhibitory Sia-recognizing Ig superfamily lectins (Siglecs) to block neutrophil and macrophage activation. We show that human platelets also express high levels of inhibitory Siglec-9 on their surface, and that GBS can engage this receptor in a Sia-dependent manner to suppress platelet activation. In a mouse i.v. infection model, antibody-mediated platelet depletion increased susceptibility to platelet-sensitive S. aureus but did not alter susceptibility to platelet-resistant GBS. Elimination of murine inhibitory Siglec-E partially reversed platelet suppression in response to GBS infection. We conclude that GBS Sia has dual roles in counteracting platelet antimicrobial immunity: conferring intrinsic resistance to platelet-derived antimicrobial components and inhibiting platelet activation through engagement of inhibitory Siglecs. We report a bacterial virulence factor for evasion of platelet-mediated innate immunity.

IL-36γ regulates mediators of tissue homeostasis in epithelial cells

IL-36 cytokines are critical regulators of mucosal inflammation and homeostasis. IL-36γ regulates the expression of inflammatory cytokines and antimicrobial proteins by gingival epithelial cells (e.g. TIGK cells). Here, we show that IL-36γ also regulates the expression of matrix metalloproteinase 9 (MMP9) and neutrophil gelatinase-associated lipocalin (NGAL), important mediators of antimicrobial immunity and tissue homeostasis in mucosal epithelia. MMP9 and NGAL were not similarly induced by IL-17 or IL-22, thus indicating the importance of IL-36γ in the regulation of MMP9 and NGAL. Mechanistically, MMP9 and NGAL expression was demonstrated to be induced in an IRAK1- and NF-κB-dependent manner. Furthermore, signaling by p38 MAP kinase may enable their expression to be independently regulated by IL-36γ. The stronger IL-36γ-inducible expression of MMP9 and NGAL in terminally differentiating TIGK cells suggests that control of their expression is associated with the maturation of the gingival epithelium. Although MMP9 and NGAL expression in epithelial cells can also be induced by bacteria, their expression in TIGK cells was not induced by the periodontal pathogen Porphyromonas gingivalis, most likely due to antagonism by the gingipain proteinase virulence factors. This study advances our understanding of how IL-36γ may promote oral mucosal immunity and tissue homeostasis, and how this may be dysregulated by bacterial pathogens.

“Deepening” Insight on Skin Aging and Anti-microbial Immunity

Skin aging is of considerable interest from various perspectives, ranging from aesthetics to cancer development. Zhang etal. (2019) elucidate an immunological consequence of aging in the adipose layer of skin. Age-dependent increases in TGF-β signaling impair fibroblast adipogenic potential that results in impaired anti-bacterial host defense.

Inducible Natural IgMs Bridge Trypanosome Lytic Factor Assembly and Parasite Recognition

Trypanosomiasis is a devastating neglected tropical disease that affects millions of livestock and thousands of humans each year. Only two subspecies of Trypanosoma brucei can cause disease in humans, while immunity to most trypanosomes is mediated in primates by HDL-associated circulating complexes called trypanosome lytic factors (TLFs) 1 and 2. Both TLFs are similar in composition, though TLF2 uniquely contains non-covalently associated IgM antibodies, the role and origin of which remain unclear. Here, we show that these TLF2-IgMs interact with TLF components and trypanosome surface proteins, including variant surface glycoprotein (VSG), likely facilitating complex biogenesis and TLF uptake into parasites. We also demonstrate that TLF2-IgMs are natural antibodies that, while present at basal concentrations in healthy individuals, are elicited by trypanosome infection in both murine models and human sleeping sickness patients. These data suggest that poly- and selfreactive natural antibodies such as TLF2-IgMs may play a role in antimicrobial immunity.

Functional crosstalk across IMD and Toll pathways: insight into the evolution of incomplete immune cascades.

In insects, antimicrobial humoral immunity is governed by two distinct gene cascades, IMD pathway mainly targeting Gram-negative bacteria and Toll pathway preferentially targeting Gram-positive bacteria, which are widely conserved among diverse metazoans. However, recent genomic studies uncovered that IMD pathway is exceptionally absent in some hemipteran lineages like aphids and assassin bugs. How the apparently incomplete immune pathways have evolved with functionality is of interest. Here we report the discovery that, in the hemipteran stinkbug Plautia stali, both IMD and Toll pathways are present but their functional differentiation is blurred. Injection of Gram-negative bacteria and Gram-positive bacteria upregulated effector genes of both pathways. Notably, RNAi experiments unveiled significant functional permeation and crosstalk between IMD and Toll pathways: RNAi of IMD pathway genes suppressed upregulation of effector molecules of both pathways, where the suppression was more remarkable for IMD effectors; and RNAi of Toll pathway genes reduced upregulation of effector molecules of both pathways, where the suppression was more conspicuous for Toll effectors. These results suggest the possibility that, in hemipterans and other arthropods, IMD and Toll pathways are intertwined to target wider and overlapping arrays of microbes, which might have predisposed and facilitated the evolution of incomplete immune pathways.

CK11, a Teleost Chemokine with a Potent Antimicrobial Activity.

CK11 is a rainbow trout (Oncorhynchus mykiss) CC chemokine phylogenetically related to both mammalian CCL27 and CCL28 chemokines, strongly transcribed in skin and gills in homeostasis, for which an immune role had not been reported to date. In the current study, we have demonstrated that CK11 is not chemotactic for unstimulated leukocyte populations from central immune organs or mucosal tissues but instead exerts a potent antimicrobial activity against a wide range of rainbow trout pathogens. Our results show that CK11 strongly inhibits the growth of different rainbow trout Gram-positive and Gram-negative bacteria, namely Lactococcus garvieae, Aeromonas salmonicida subsp. salmonicida, and Yersinia ruckeri and a parasitic ciliate Ichthyophthirius multifiliis Similarly to mammalian chemokines and antimicrobial peptides, CK11 exerted its antimicrobial activity, rapidly inducing membrane permeability in the target pathogens. Further transcriptional studies confirmed the regulation of CK11 transcription in response to exposure to some of these pathogens in specific conditions. Altogether, our studies related to phylogenetic relations, tissue distribution, and biological activity point to CK11 as a potential common ancestor of mammalian CCL27 and CCL28. To our knowledge, this study constitutes the first report of a fish chemokine with antimicrobial activity, thus establishing a novel role for teleost chemokines in antimicrobial immunity that supports an evolutionary relationship between chemokines and antimicrobial peptides.

IL-22 Preserves Gut Epithelial Integrity and Promotes Disease Remission during Chronic Salmonella Infection.

The cytokine IL-22 is rapidly induced at barrier surfaces where it regulates host-protective antimicrobial immunity and tissue repair but can also enhance disease severity in some chronic inflammatory settings. Using the chronic Salmonella gastroenteritis model, Ab-mediated neutralization of IL-22 impaired intestinal epithelial barrier integrity and, consequently, exaggerated expression of proinflammatory cytokines. As disease normally resolved, neutralization of IL-22 caused luminal narrowing of the cecum-a feature reminiscent of fibrotic strictures seen in Crohn disease patients. Corresponding to the exaggerated immunopathology caused by IL-22 suppression, Salmonella burdens in the gut were reduced. This enhanced inflammation and pathogen clearance was associated with alterations in gut microbiome composition, including the overgrowth of Bacteroides acidifaciens Our findings thus indicate that IL-22 plays a protective role by limiting infection-induced gut immunopathology but can also lead to persistent pathogen colonization.

Сondition of indicators of antimicrobial resistance in patients with allergic dermatoses complicated by staphylococcal infection, depending on the severity of the diseases

The aim of the work: To determine and analyse the results of indicators of antimicrobial immunity in patients with an uncomfortable and aggravated course of allergic dermatoses using auto-serums and auto-strains of Staphylococcus aureus obtained from patients with atopic dermatitis (AD) and true eczema (ТE).Methods of research: In the study, 107 patients were examined for AD and TE who were hospitalized in the Department of Dermatology of the SЕ “Institute of Dermatology on Venereology of the National Academy of Medical Sciences of Ukraine” in 2016-2019, which included an analysis of complaints and medical history data, an assessment of the severity of the disease according to the SCORAD scale and EASI, conducting general clinical, bacteriological and immunological studies.Examination of patients was carried out during an exacerbation of the disease.Results: As a result of the studies, it was found that changes in immunological reactivity in patients with AD were more pronounced than in patients with TE, which was manifested by significant inhibition of almost all indicators of the functional activity of blood leukocytes (both indicators of the phagocytic reaction, and spontaneous and induced HCT test) from moderate to severe, this is especially noticeable in the group of patients with severe course of AD.It was shown that in patients with AD and TE in the acute stage, the formation of a secondary immunodeficiency state is observed, which is manifested by a decrease in the leukocyte phagocytic activity, which may be an indication for inclusion in the complex treatment of immunocorrective therapy

Thymosin participates in antimicrobial immunity in zebrafish

Thymosin hormones, which were shown to be involved in immune system development and differentiation in previous studies, have antimicrobial functions in different animals. Zebrafish are a useful model for immunology research. Although thymosin has been reported to be involved in the embryonic development of zebrafish, it is necessary to uncover the antimicrobial function of thymosin in zebrafish. In this study, we expressed thymosin β (Tβ) in zebrafish in vitro and studied its antimicrobial function. The Tβ protein consists of 45 amino acids and is conserved among its family members, especially the actin-binding motif (LKKTET). Tβ was expressed in all tested tissues and was highly expressed in the brain, liver and hindgut. After Aeromonas hydrophila challenge, the Tβ transcript level increased in the skin, liver, kidney, spleen, thymus, foregut, gills and midgut. Purified recombinant thymosin β (rTβ) protein was used to study the antimicrobial mechanism. rTβ could inhibit the growth of Staphylococcus aureus, Aeromonas hydrophila, Vibrio anguillarum, Pseudomonas aeruginosa and Klebsiella pneumoniae. rTβ also binds to and agglutinates certain bacteria. Further study showed that rTβ could combine with the polysaccharides from gram-negative and gram-positive bacterial walls. All results suggested that the Tβ of zebrafish plays a significant role in innate antibacterial immune responses.

Synthetic CpG-ODN rapidly enriches immune compartments in neonatal chicks to induce protective immunity against bacterial infections

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) induce innate immunity against bacterial infections. Despite recent advances, how CpG-ODN alone protects against bacterial infections remained elusive. Here, we report for the first time, to our knowledge, that CpG-ODN orchestrates anti-microbial protective immunity by inducing a rapid enrichment of various immune compartments in chickens. In this study, eighteen-day-old embryonated eggs were injected with either 50 µg of CpG-ODN or saline (~n = 90 per group). In the first experiment, four days after CpG-ODN treatment, chicks were challenged subcutaneously with a virulent strain of Escherichia coli (E. coli) and mortality was monitored for 8 days. We found significant protection, and reduced clinical scores in CpG-ODN treated chicks. To gain insights into mechanisms of protection induced by CpG-ODN, first we investigated cytokine expression kinetics elicited by CpG-ODN. The spleen and lung were collected from embryos or chicks (n = 3–4 per group) at 10 time points post-CpG-ODN inoculation. Multiplex gene analysis (interleukin (IL)-1, IL-4, IL-6, IL-10, IL-18, interferon (IFN)-γ, IFN-α, and lipopolysaccharide induced tumor necrosis factor (LITAF), revealed a significantly higher expression of pro-inflammatory cytokines following CpG-ODN treatment compared to the saline controls. In our study, LITAF stands out in the cytokine profiles of spleen and lungs, underscoring its role in CpG-ODN-induced protection. The third experiment was designed to examine the effects of CpG-ODN on immune cell populations in spleen, lungs, and thymus. Flow cytometry analysis was conducted at 24, 48 and 72 hrs (thymus only collected at 72 hr) after CpG-ODN administration to examine the changes in CD4+ and CD8+ T-cell subsets, monocyte/macrophage cell populations and their expression of maturation markers (CD40 and CD86). Flow cytometry data indicated a significant enrichment of macrophages, CD4+ and CD8+ T-cell subsets in both spleen and lungs of CpG-ODN treated embryos and chicks. Macrophages in spleen and lungs showed an upregulation of CD40 but not CD86, whereas thymocytes revealed significantly high CD4 and CD8 expression. Overall, the present study has demonstrated that CpG-ODN provides protection in neonatal chicks against E. coli infection not only by eliciting cytokine responses and stimulating immune cells but also through enriching immunological niches in spleen and lungs.

Роль аутофагии при инфекциях

The autophagy refers to normal physiological processes, aimed at regulating the size of cell populations by maintaining a balance between cell survival and death. Autophagy allows cells to recycle damaged molecules and organelles, to survive and to renew in conditions of stress or starvation. Autophagy attracts special attention not only in connection with homeostatic functions but also the important role that this process plays in antimicrobial immunity. In bacterial and viral infections, the autophagy is often induced as a way of the host organism protection against invaders or a mechanism of the pathogen's survival strategy. In recent years, the results of experimental studies have been published, indicating the critical role of autophagy in the regulation of the immune response. Autophagy as a factor of antimicrobial immunity can help in clearance the body from pathogens and, at the same time, provides a cross-presentation of microbial antigens to induce an antimicrobial immune response. Along with this, it is established that many pathogens in the process of evolution have acquired virulence factors that can interfere with the autophagy pathway, perverting its initial protective role and reducing the antimicrobial resistance.

Hypoxia-dependent control of the activity of innate antimicrobial immunity in patients with dentin caries

To study interrelation of maintenance of α-defensins 1-3 and a hypoxia-inducible factor 1-alpha (HIF-1α) in gingival liquid of patients with caries. 75 patients with the diagnosis dentine caries were enrolled in the study and divided into two groups: in group 1 (n=30) caries was diagnosed in earlier untreated tooth, the 2nd group (n=45) included patients with the recurrence of carious process (in earlier treated tooth). Controls involved 25 caries-free individuals. The level of α-defensins 1-3 was studied in gingival fluid by ELISA method. The level of α-defensins 1-3 and antimicrobic peptide in gingival liquid in group 2 was 28 and 36% higher than in the 1st group, correspondingly (p<0.001). Concentration of HIF-1α in gingival liquid in the 2nd group was almost twice higher (p<0.001) than in group 1 and 82% higher than in controls (p<0.001), while in group 1 it decreased by 11% when compared to controls (p<0.001). All controls showed a close correlation between the level of α-defensins 1-3 and HIF-1α in gingival fluid (R=0.78, p<0.001), not observed in group 1 (R=0.32, p>0.05) but statistically significant in group 2 (R=0.78, p<0.001). Thus, the recurrence of carious process in caries-associated tooth is associated with the hypoxia-dependent activation of a congenital antimicrobial immunity by means of accumulation of HIF-1α and pronounced increase of α-defensins 1-3 in gingival fluid.

Cathelicidins In Humans And Animals

Abstract Cathelicidins are Important immunological peptides – HDPs (Host Defense Peptides) with high biological activity in mammals, including human and vertebrate animals. These evolutionary ancient molecules in these organisms are natural elements of antimicrobial, antiviral, antifungal and antiparasitic immunity against which germs and parasites have not developed immunity, which makes them alternatives to antibiotics. Catelicidins in human and vertebrates affect the germs and parasites directly and indirectly by activating the immune system. 1.What are immune peptides. 2. Cathelicidins. 2.1. Catelicidins in humans. 2.2. Cathelicidins in animals. 3. Summary

Analyzing Antigen Recognition by Natural Killer T Cells.

Natural killer T (NKT) cells are a subset of T lymphocytes that recognize a wide variety of lipid antigens presented by the atypical MHC class I molecule CD1d. NKT cells exhibit rapid activation after recognition of cognate antigens, secrete abundant amounts of T helper (Th) 1, Th2, and Th17 cytokines within hours of activation and shape the immune response through subsequent activation of dendritic, NK, T, and B cells. NKT cells therefore play central roles in antimicrobial and anticancer immunity and in the modulation of various autoimmune disorders. Consequently, recent research has focused on the discovery of microbial and self-antigens involved in NKT cell activation. In this chapter, we will discuss different strategies for studying antigen recognition by NKT cells including CD1d tetramer-based approaches and in vitro assays characterizing NKT cell activation in response to lipid antigen presentation. While Toll-like receptor (TLR) agonists and cytokines such as IL-12 are critical for NKT cell activation in vivo, particularly in the context of microbial infection, methods for detection of TLR- and cytokine-dependent NKT cell activation will not be discussed in this section.

Phenoloxidase activity and haemolymph cytology in honeybees challenged with a virus suspension (deformed wings virus DWV) or phosphate buffered suspension (PBS)

ABSTRACT: The innate immune system of honeybees mainly consists in antimicrobial peptides, cellular immunity and melanisation. In order to investigate the immune response of honeybees to immune stressors, three stress degrees were tested. Newly emerged bees naturally DWV-infected were collected from a Varroa mite-free apiary and divided into three experimental groups: naturally DWV infected bees, PBS injected bees, and artificially DWV super infected bees. Phenoloxidase activity and haemolymph cellular subtype count were investigated. Phenoloxidase activity was highest (P&lt;0.05) in DWV-superinfected bees, and the haemocyte population differed within the three observed groups. Although, immune responses following DWV infection have still not been completely clarified, this investigation sheds light on the relation between cell immunity and the phenoloxidase activity of DWV-naturally infected honeybees exposed to additional stress such as injury and viral superinfection.

Coronin-1, King of Alloimmunity

Defining pathways that differentially regulate graft-reactive versus anti-microbial Tcell responses could facilitate more precise manipulation of immune responses in the context of organ and tissue transplantation. Here, Jayachandran etal. (2019) identify a coronin-1-PDE4-cAMP axis that, when perturbed, results in the induction of transplantation tolerance while maintaining anti-microbial immunity.