Two intestinal microbiota-derived metabolites, deoxycholic acid and butyrate, synergize to enhance host defense peptide synthesis and alleviate necrotic enteritis

Background Necrotic enteritis(NE)is a major enteric disease in poultry,yet effective mitigation strategies remain elusive.Deoxycholic acid(DCA)and butyrate,two major metabolites derived from the intestinal microbiota,have independently been shown to induce host defense peptide(HDP)synthesis.However,the potential synergy between these two compounds remains unexplored.Methods To investigate the possible synergistic effect between DCA and butyrate in regulating HDP synthesis and barrier function,we treated chicken HD11 macrophage cells and jejunal explants with DCA and sodium butyrate(NaB),either individually or in combination,for 24 h.Subsequently,we performed RNA isolation and reverse transcrip-tion-quantitative PCR to analyze HDP genes as well as the major genes associated with barrier function.To further determine the synergy between DCA and NaB in enhancing NE resistance,we conducted two independent trials with Cobb broiler chicks.In each trial,the diet was supplemented with DCA or NaB on the day-of-hatch,followed by NE induction through sequential challenges with Eimeria maxima and Clostridium perfringens on d 10 and 14,respectively.We recorded animal mortality after infection and assessed intestinal lesions on d 17.The impact of DCA and NaB on the microbiota in the ileum and cecum was evaluated through bacterial 16S rRNA gene sequencing.Results We found that the combination of DCA and NaB synergistically induced multiple HDP genes in both chicken HD11 cells and jejunal explants.Additionally,the gene for claudin-1,a major tight junction protein,also exhibited synergistic induction in response to DCA and NaB.Furthermore,dietary supplementation with a combination of 0.75 g/kg DCA and 1 g/kg NaB led to a significant improvement in animal survival and a reduction in intestinal lesions compared to either compound alone in a chicken model of NE.Notably,the cecal microbiota of NE-infected chickens showed a marked decrease in SCFA-producing bacteria such as Bacteroides,Faecalibacterium,and Cuneatibacter,with lactobacilli becoming the most dominant species.However,supplementation with DCA and NaB largely restored the intestinal microbiota to healthy levels.Conclusions DCA synergizes with NaB to induce HDP and claudin-1 expression and enhance NE resistance,with potential for further development as cost-effective antibiotic alternatives.

The dual antimicrobial and immunomodulatory roles of host defense peptides and their applications in animal production

Host defense peptides(HDPs)are small molecules with broad-spectrum antimicrobial activities against infectious bacteria,viruses,and fungi.Increasing evidence suggests that HDPs can also indirectly protect hosts by modulating their immune responses.Due to these dual roles,HDPs have been considered one of the most promising antibiotic substitutes to improve growth performance,intestinal health,and immunity in farm animals.This review describes the antimicrobial and immunomodulatory roles of host defense peptides and their recent applications in animal production.

Discovery of natural products capable of inducing porcine host defense peptide gene expression using cell-based high throughput screening

Background:In-feed antibiotics are being phased out in livestock production worldwide.Alternatives to antibiotics are urgently needed to maintain animal health and production performance.Host defense peptides(HDPs)are known for their broad-spectrum antimicrobial and immunomodulatory capabilities.Enhancing the synthesis of endogenous HDPs represents a promising antibiotic alternative strategy to disease control and prevention.Methods:To identify natural products with an ability to stimulate the synthesis of endogenous HDPs,we performed a high-throughput screening of 1261 natural products using a newly-established stable luciferase reporter cell line known as IPEC-J2/pBD3-luc.The ability of the hit compounds to induce HDP genes in porcine IPEC-J2 intestinal epithelial cells,3D4/31 macrophages,and jejunal explants were verified using RT-qPCR.Augmentation of the antibacterial activity of porcine 3D4/31 macrophages against a Gram-negative bacterium(enterotoxigenic E.coli)and a Gram-positive bacterium(Staphylococcus aureus)were further confirmed with four selected HDP-inducing compounds.Results:A total of 48 natural products with a minimum Z-score of 2.0 were identified after high-throughput screening,with 21 compounds giving at least 2-fold increase in luciferase activity in a follow-up dose-response experiment.Xanthohumol and deoxyshikonin were further found to be the most potent in inducing pBD3 mRNA expression,showing a minimum 10-fold increase in IPEC-J2,3D4/31 cells,and jejunal explants.Other compounds such as isorhapontigenin and calycosin also enhanced pBD3 mRNA expression by at least 10-fold in both IPEC-J2 cells and jejunal explants,but not 3D4/31 cells.In addition to pBD3,other porcine HDP genes such as pBD2,PG1-5,and pEP2C were induced to different magnitudes by xanthohumol,deoxyshikonin,isorhapontigenin,and calycosin,although clear gene-and cell type-specific patterns of regulation were observed.Desirably,these four compounds had a minimum effect on the expression of several representative inflammatory cytokine genes.Furthermore,when used at HDP-inducing concentrations,these compounds showed no obvious direct antibacterial activity,but significantly augmented the antibacterial activity of 3D4/31 macrophages(P<0.05)against both Gram-negative and Gram-positive bacteria.Conclusions:Our results indicate that these newly-identified natural HDP-inducing compounds have the potential to be developed as novel alternatives to antibiotics for prophylactic and therapeutic treatment of infectious diseases in livestock production.

Geographically Distinct Expression Profile of Host Defense Peptides in the Skin of the Chinese Odorous Frog, Odorrana margaretae

Odorrana margaretae （Anura： Ranidae） is widely distributed in the southern provinces of China. Previously, 72 antimicrobial peptides （AMPs） belonging to 21 families were identified from the skin of O. margaretae, which were captured in the Hunan province. In the present study, five O. margaretae frogs were captured from the Guizhou province and a total of 28 cDNAs encoding 17 host defense peptides （HDPs） belonging to 14 families were cloned from the skin cDNA library of O. margaretae. Among the 17 HDPs, only one （brevinin-1-Omar5） had been characterized. The distinct HDP expression profiles for O. margaretae in the previous and present study may be attributed to the environmental differences between the sampling locations and the genetic divergence among O. margaretae populations. Besides, 11 of the 17 HDPs identified in the present study were novel for ranids. In order to understand their roles in host defense reactions, three HDPs （odorranain-H-OM1, odorranain-M-OM and ranatuerin-2-OM）, which possess low sequence similarity with the known amphibian HDPs, were selected for further chemical synthesis and functional analysis. Odorranain-H-OM1 showed direct antimicrobial activity against bacteria and fungi. Odorranain-M-OM exhibited concentration-dependent anti-oxidant activity. Ranatuerin-2-OM showed lectin-like activity and could strongly hemagglu -tinate human intact erythrocytes with or without the presence of Ca2＋. The diverse activities of HDPs implied that they may play different roles in host defense reactions of O. margaretae.

Quorum Sensing:An Emerging Role for Vibrio Infection and Host Defense

Quorum sensing(QS)is a mechanism that allows bacteria to regulate various physiological and biochemical functions by secreting,sensing and responding to signaling molecules called autoinducers(AIs).In Vibrio species,QS plays a crucial role in modulating different biological characteristics.QS can influence the formation of biofilms,which are communities of bacteria encased in a protective matrix.It also controls flagella formation and motility,ensuring that Vibrio spp.can move efficiently in response to environmental cues.Additionally,QS in Vibrio spp.regulates the production of different virulence factors based on cell density.This enables the bacteria to adjust their virulence strategies accordingly,enhancing pathogenicity.QS also influences the interaction between Vibrio spp.and their host.Following infection by Vibrio spp.,QS can affect the host immune response and colonization processes.Understanding the role of QS in these interactions is crucial for unraveling the complex dynamics between Vibrio spp.and the host.In summary,research on QS in Vibrio spp.has revealed its significance in regulating various biological phenotypes,controlling virulence factor production and affecting host defense.It provides valuable insights into the intricate mechanisms underlying microbial behavior,host adaptation and Vibrio spp.pathogenesis.

Host defense peptide-mimicking peptide polymer-based antibacterial hydrogel enables efficient healing of MRSA-infected wounds

Wound infections are a compelling health issue caused by the invasion and proliferation of pathogens in wound sites.Antibioticloaded hydrogels are widely used to achieve anti-infectious wound healing.However,due to the quick emergence of drugresistant bacteria,such as methicillin-resistant Staphylococcus aureus(MRSA),wound infection has been a formidable challenge to human health.To address MRSA-infected wounds,an antibacterial peptide polymer-loaded hyaluronic acid(HA)hydrogel(Gel-HA@P)is prepared.The peptide polymer is designed to mimic host defense peptides as the antibiotic alternative showing potent antibacterial activity,low susceptibility to drug resistance and good stability against proteolysis.HA is biocompatible and biodegradable hydrogel substrate as a primary constituent of the extracellular matrix and suitable for cell migration and wound healing.Gel-HA@P shows potent activity against MRSA in vitro and in vivo,low toxicity during the treatment and promotes the wound healing in vivo.This design has proven to be an effective and antibiotic-free strategy to enable the healing of MRSA-infected wounds.

Host defense peptide-mimickingβ-peptide polymer displaying strong antibacterial activity against cariogenic Streptococcus mutans

Cariogenic Streptococcus mutans(S.mutans)is a leading cause of bacterial-induced oral diseases.Current strategies to kill bacteria based on Host defense peptide(HDP)mimicking polymers hold promise to treat oral bacterial infection.Here,we explore the impact of hydrophobic subunit and chain length variation on the antibacterial and antibiofilm activity ofβ-peptide polymers.The physicochemical and biological prop-erties,such as the toxicity,the antibacterial activity,and the effect on bacterial transcription ofβ-peptide polymers,were systematically investigated with numerous techniques.The results exhibited that the op-timalβ-peptide polymer has low toxicity towards human periodontal ligament fibroblasts,andβ-peptide polymers(especially P3)have more excellent antibacterial activity against S.mutans than metronidazole.In addition,β-peptide polymers inhibited the reversible and irreversible bacterial adhesion during the formation of biofilms.The polymer can promote biofilm dispersion by decreasing the hydrophobicity of bacterial cells after adhering to cell surfaces.Analysis of the transcriptome for S.mutans treated withβ-peptide polymers demonstrated thatβ-peptide polymers could reduce the cariogenicity of S.mutans by impacting the transcription of the energy and acid metabolism-related genes.β-peptide polymers are promising antimicrobial agents in clinical dentistry due to their high antibacterial efficiency and low tox-icity.

Dietary modulation of endogenous host defense peptide synthesis as an alternative approach to in-feed antibiotics

Traditionally, antibiotics are included in animal feed at subtherapeutic levels for growth promotion and disease prevention.However, recent links between in-feed antibiotics and a rise in antibiotic-resistant pathogens have led to a ban of all antibiotics in livestock production by the European Union in January 2006 and a removal of medically important antibiotics in animal feeds in the United States in January 2017.An urgent need arises for antibiotic alternatives capable of maintaining animal health and productivity without triggering antimicrobial resistance.Host defense peptides(HDP) are a critical component of the animal innate immune system with direct antimicrobial and immunomodulatory activities.While in-feed supplementation of recombinant or synthetic HDP appears to be effective in maintaining animal performance and alleviating clinical symptoms in the context of disease, dietary modulation of the synthesis of endogenous host defense peptides has emerged as a cost-effective,antibiotic-alternative approach to disease control and prevention.Several different classes of smallmolecule compounds have been found capable of promoting HDP synthesis.Among the most efficacious compounds are butyrate and vitamin D.Moreover, butyrate and vitamin D synergize with each other in enhancing HDP synthesis.This review will focus on the regulation of HDP synthesis by butyrate and vitamin D in humans, chickens, pigs, and cattle and argue for potential application of HDP-inducing compounds in antibiotic-free livestock production.

Gut microbiota metabolite regulation of host defenses at mucosal surfaces:implication in precision medicine

The gut microbiota has a well-established role in the regulation of host homeostasis.Multiple factors control the composition and function of the microbiota.The westernization of diet,a shift away from nutrient-dense foods toward diets high in saturated fats,has been implicated in the rise of chronic inflammatory diseases such as inflammatory bowel disease(IBD).Diet is critical in the development and maintenance of a healthy microbiome,where dietary fiber(found in the highest amounts in fruits,vegetables,and legumes)is metabolized by the microbiome.In turn,the bacterial metabolites of dietary fiber,short chain fatty acids(SCFAs),regulate gut homeostasis.SCFAs engage G-protein coupled receptors(GPRs)and act as histone deacetylase inhibitors(HDACi)to module epithelial and immune cell functions in the intestines,where they generally promote an anti-inflammatory state.This review highlights the functions of SCFAs and their roles in the pathogenesis of IBD to provide insights into their potential therapeutic application for the treatment of IBD for the purposes of precision medicine.

Breaking or following the membrane-targeting mechanism:Exploring the antibacterial mechanism of host defense peptide mimicking poly(2-oxazoline)s

Peptides exert important biological functions but their application is hindered by their susceptibility to proteolysis and poor stability in vivo.Thus,functional peptide mimics have drawn a great deal of attention to address this challenge.Poly(2-oxazoline)s,a class of biocompatible and proteolysis-resistant polymer,can work as host defense peptide mimics without following the general membrane-targeting mechanism as shown in our previous work.This observation encouraged us to figure out if poly(2-oxazoline)s are special and break the general membrane-targeting mechanism of host defense peptides and their mimics.In this study,we aimed at the connection between structure and antibacterial mechanism of poly(2-oxazoline)s.A new γ-aminobutyric acid(GABA)-pendent poly(2-oxazoline)was synthesized and investigated to compare with glycine-pendent poly(2-oxazoline)in our previous study,with the former polymer has two extra CH2 groups in the sidechain to increase the hydrophobicity and amphiphilicity.Membrane depolarization assay suggested that incorporating two more CH2 groups into the sidechain of poly(2-oxazoline)resulted in a mechanism switch from DNA-targeting to membrane-targeting,which was supported by the slow time-kill kinetics and slightly distorted and sunken membrane morphology.Besides,GABA-pendent poly(2-oxazoline)showed potent activity against methicillin-resistant S.aureus and low hemolysis on human red blood cells.Moreover,repeated use of the antimicrobial poly(2-oxazoline)did not stimulate bacteria to obtain resistance,which was an obvious advantage of membrane-targeting antimicrobial agents.

SiO_(2) prompts host defense against Acinetobacter baumannii infection by mTORC1 activation

Host-pathogen interactions in the setting of chronic pulmonary inflammation remain unclear,and the occurrence of pneumonia is increased in patients with chronic obstructive pulmonary disease who use immunosuppressive drugs.We performed Acinetobacter baumannii infection in mice with chronic pulmonary inflammation after intranasal administration of SiO_(2) and found SiO_(2) treatment increased host defense against A.baumannii infection.Innate immune responses initiated by NF-κB,type 1 interferon,NLRP3 and AIM2 inflammasomes were dispensable for SiO_(2)-mediated host defense.SiO_(2)treatment activated the mTORC1 signaling,and mTORC1 was crucial for host defense against A.baumannii infection.Our study highlights the protective role of mTORC1 signaling in host defense against bacterial infection,offers novel insights into understanding the mechanisms of immunosuppressive drug-related pneumonia,and provides potential host-directed therapeutics to treat bacterial infections.

Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury

Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”

Transcriptome and metabolome analysis reveal that oral secretions from Helicoverpa armigera and Spodoptera litura influence wound-induced host response in cotton

Cotton(Gossypium hirsutum)is an important fiber crop worldwide.Insect attack causes cotton yield and quality losses.However,little is known about the mechanism of cotton response to insect attack.We simulated insect feeding by applying insect oral secretions(OS)to wounds,and combined transcriptome and metabolome analysis to investigate how OS from two major pest species(Helicoverpa armigera and Spodoptera litura)affect cotton defense responses.We found that respectively 12,668 and 13,379 genes were differentially expressed in comparison with wounding alone.On addition of OS,the jasmonic acid signaling pathway was rapidly and strongly induced,whereas genes involved in salicylic acid biosynthesis were downregulated.On constructing a coexpression gene network,we identified a hub gene encoding a leucine-rich repeat receptor kinase that may play an important role in early signal recognition and transduction.OS from the two insect species altered the abundance of flavonoid-related compounds in different patterns.Gossypol remained in lower concentration after OS application than after wounding alone,suggesting a suppressive effect of OS on cotton defense response.This study illustrated transcriptional and metabolic changes of cotton in responding to OS from two chewing insect species,identified potential key response genes,and revealed evidence for OS inhibition of wounding-induced cotton defense response.

Impacts of brood parasitism by shiny cowbird Molothrus bonariensis on the breeding success of a small host, the black-backed water tyrant Fluvicola albiventer

The shiny cowbird Molothrus bonariensis parasitizes many species with different life-history traits and has a detrimental effect on the survival of the progeny of the hosts.In response,hosts have developed numerous antiparasitic defenses.Here,we examined the effects of brood parasitism by shiny cowbird on the clutch and brood sizes(83 nests)in a small host,the black-backed water tyrant Fluvicola albiventer.We also studied whether the death of parasite nestlings was related to the care of the foster parents and whether the host had any antiparasitic defense against the shiny cowbird.Our results indicate that brood parasitism significantly decreased the host hatching and fledging successes.The majority of nest failures(57%)were caused by brood parasitism.Shiny cowbird parasitism occurred in 52%of nests and the intensity of parasitism was 1.23±0.53 eggs per parasitized nest.Of the total host eggs,54%were damaged.During the incubation stage,20 nests(47%)were abandoned because of egg punctures by shiny cowbirds females.Only two parasitic fledglings were recorded,while the remaining nestlings either died from starvation(n=12)or predation(n=3).Foster parents abandoned parasitic nestlings between 5 and 10 days old.Our findings demonstrate that the shiny cowbird has very low rates of fledging success when parasitizing black-backed water tyrant.Also,parasitism had a high reproductive cost in the black-backed water tyrant because a very low proportion(7%)of the parasitized nests(n=43)were successful.

Complement and its role in innate and adaptive immune responses

The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.

Role of nutritional status and nutritional support in outcome of hepatitis B virus-associated acute-on-chronic liver failure

BACKGROUNDHepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is animportant type of liver failure in Asia. There is a direct relationship between HBVACLFand gastrointestinal barrier function. However, the nutritional status ofHBV-ACLF patients has been poorly studied.AIMTo investigate the nutritional risk and nutritional status of HBV-ACLF patientsand evaluated the impact of nutritional support on the gastrointestinal barrier and28-d mortality.METHODSNutritional risk screening assessment and gastrointestinal barrier biomarkers ofpatients with HBV-ACLF (n = 234) and patients in the compensatory period ofliver cirrhosis (the control group) (n = 234) were compared during the periodbetween 2016 and 2018. Changes were analyzed after nutritional support in HBVACLFpatients. Valuable biomarkers have been explored to predict 28-d death.The 28-d survival between HBV-ACLF patients with nutritional support (n = 234)or no nutritional support (2014-2016) (n = 207) was compared.RESULTSThe nutritional risk of the HBV-ACLF patients was significantly higher than thatof the control group. The nutritional intake of the patients with HBV-ACLF waslower than that of the control group. The decrease in skeletal muscle and fatcontent and the deficiency of fat intake were more obvious (P < 0.001). Thecoccus-bacillus ratio, secretory immunoglobulin A, and serum D-lactate weresignificantly increased in HBV-ACLF patients. The survival group had a lowernutritional risk, lower D-lactate, and cytokine levels (endotoxin, tumor necrosisfactor alpha, interleukin-10, and interleukin-1). Interleukin-10 may be a potentialpredictor of death in HBV-ACLF patients. The 28-d survival of the nutritionalsupport group was better than that of the non-nutritional support group (P =0.016).CONCLUSIONPatients with HBV-ACLF have insufficient nutritional intake and high nutritionalrisk, and their intestinal barrier function is impaired. Individualized and dynamicnutritional support is associated with a better prognosis of 28-d mortality in HBVACLFpatients.

Human ribonuclease 9,a member of ribonuclease A superfamily,specifically expressed in epididymis,is a novel sperm-binding protein

To explore the functions of human ribonuclease 9(RNase 9),we constructed a mammalian fusion expression vector pcDNA-hRNase9,prepared recombinant human RNase 9-His fusion protein from HEK293T cells and determined its N-terminal amino acid sequences.According to the determined mature protein,recombinant human RNase 9 was prepared in E.coli.Ribonucleolytic activity and antibacterial activity of recombinant human RNase 9 were detected,and the distribution of human RNase 9 on tissues and ejaculated spermatozoa and in vitro capacitated spermatozoa were analyzed via indirect immunofluorescence assay.The results showed that recombinant human RNase 9 did not exhibit detectable ribonucleolytic activity against yeast tRNA,but exhibited antibacterial activity,in a concentration/time dependent manner,against E.coli.Immunofluorescent analyses showed that the predicted human RNase 9 was present throughout the epididymis,but not present in other tissues examined,and human RNase 9 was also present on the entire head and neck regions of human ejaculated spermatozoa and in vitro capacitated spermatozoa.These results suggest that human RNase 9 may play roles in host defense of male reproductive tract.

Regulation of innate immune responses by rabies virus

Rabies virus(RABV)is an infectious and neurotropic pathogen that causes rabies and infects humans and almost all warm-blooded animals,posing a great threat to people and public safety.It is well known that innate immunity is the critical first line of host defense against viral infection.It monitors the invading pathogens by recognizing the pathogen-associated molecular patterns and danger-associated molecular patterns through pattern-recognition receptors,leading to the production of type I interferons(IFNα/β),inflammatory cytokines,and chemokines,or the activation of autophagy or apoptosis to inhibit virus replication.In the case of RABV,the innate immune response is usually triggered when the skin or muscle is bitten or scratched.However,RABV has evolved many ways to escape or even hijack innate immune response to complete its own replication and eventually invades the central nervous system(CNS).Once RABV reaches the CNS,it cannot be wiped out by the immune system or any drugs.Therefore,a better understanding of the interplay between RABV and innate immu-nity is necessary to develop effective strategies to combat its infection.Here,we review the innate immune responses induced by RABV and illustrate the antagonism mechanisms of RABV to provide new insights for the control of rabies.

Tissue expression and developmental regulation of chicken cathelicidin antimicrobial peptides

Cathelicidins are a major family of antimicrobial peptides present in vertebrate animals with potent microbicidal and immunomodulatory activities. Four cathelicidins, namely fowlicidins 1 to 3 and cathelicidin B1, have been identified in chickens. As a first step to understand their role in early innate host defense of chickens, we examined the tissue and developmental expression patterns of all four cathelicidins. Real-time PCR revealed an abundant expression of four cathelicidins throughout the gastrointestinal, respiratory, and urogenital tracts as well as in all primary and secondary immune organs of chickens. Fowlicidins 1 to 3 exhibited a similar tissue expression pattern with the highest expression in the bone marrow and lung, while cathelicidin B1 was synthesized most abundantly in the bursa of Fabricius. Additionally, a tissue-specific regulatory pattern was evident for all four cathelicidins during the first 28 days after hatching. The expression of fowlicidins 1 to 3 showed an age-dependent increase both in the cecal tonsil and lung, whereas all four cathelicidins were peaked in the bursa on day 4 after hatching, with a gradual decline by day 28. An abrupt augmentation in the expression of fowlicidins 1 to 3 was also observed in the cecum on day 28, while the highest expression of cathelicidin B1 was seen in both the lung and cecal tonsil on day 14. Collectively, the presence of cathelicidins in a broad range of tissues and their largely enhanced expression during development are suggestive of their potential important role in early host defense and disease resistance of chickens.

Roles and relevance of mast cells in infection and vaccination

In addition to their well-established role in allergy mast cells have been described as contributing to functional regulation of both innate and adaptive immune responses in host defense. Mast cells are of hematopoietic origin but typically complete their differentiation in tissues where they express immune regulatory functions by releasing diverse mediators and cytokines. Mast cells are abundant at mucosal tissues which are portals of entry for common infectious agents in addition to allergens. Here, we review the current understanding of the participation of mast cells in defense against infection. We also discuss possibilities of exploiting mast cell activation to provide adequate adjuvant activity that is needed in high-quality vaccination against infectious diseases.