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Frontiers in Cellular and Infection... 2022Tick sialome is comprised of a rich cocktail of bioactive molecules that function as a tool to disarm host immunity, assist blood-feeding, and play a vibrant role in... (Review)
Review
Tick sialome is comprised of a rich cocktail of bioactive molecules that function as a tool to disarm host immunity, assist blood-feeding, and play a vibrant role in pathogen transmission. The adaptation of the tick's blood-feeding behavior has lead to the evolution of bioactive molecules in its saliva to assist them to overwhelm hosts' defense mechanisms. During a blood meal, a tick secretes different salivary molecules including vasodilators, platelet aggregation inhibitors, anticoagulants, anti-inflammatory proteins, and inhibitors of complement activation; the salivary repertoire changes to meet various needs such as tick attachment, feeding, and modulation or impairment of the local dynamic and vigorous host responses. For instance, the tick's salivary immunomodulatory and cement proteins facilitate the tick's attachment to the host to enhance prolonged blood-feeding and to modulate the host's innate and adaptive immune responses. Recent advances implemented in the field of "omics" have substantially assisted our understanding of host immune modulation and immune inhibition against the molecular dynamics of tick salivary molecules in a crosstalk between the tick-host interface. A deep understanding of the tick salivary molecules, their substantial roles in multifactorial immunological cascades, variations in secretion, and host immune responses against these molecules is necessary to control these parasites. In this article, we reviewed updated knowledge about the molecular mechanisms underlying host responses to diverse elements in tick saliva throughout tick invasion, as well as host defense strategies. In conclusion, understanding the mechanisms involved in the complex interactions between the tick salivary components and host responses is essential to decipher the host defense mechanisms against the tick evasion strategies at tick-host interface which is promising in the development of effective anti-tick vaccines and drug therapeutics.
Topics: Animals; Immunity; Proteins; Saliva; Ticks
PubMed: 35372098
DOI: 10.3389/fcimb.2022.809052 -
Clinical and Experimental Immunology Nov 2018Dipeptidyl peptidase 4 (DPP4, CD26) is a serine protease that is expressed constitutively by many haematopoietic and non-haematopoietic tissues. It exists as a... (Review)
Review
Dipeptidyl peptidase 4 (DPP4, CD26) is a serine protease that is expressed constitutively by many haematopoietic and non-haematopoietic tissues. It exists as a membrane-associated protein, as well as in an active, soluble form (herein called sDPP4), present at high concentrations in bodily fluids. Despite the proposed use of sDPP4 as a biomarker for multiple diseases, its cellular sources are not well defined. Here, we report that individuals with congenital lymphocyte immunodeficiency had markedly lower serum concentrations of sDPP4, which were restored upon successful treatment and restoration of lymphocyte haematopoiesis. Using irradiated lymphopenic mice and wild-type to Dpp4 reciprocal bone marrow chimeric animals, we found that haematopoietic cells were a major source of circulating sDPP4. Furthermore, activation of human and mouse T lymphocytes resulted in increased sDPP4, providing a mechanistic link between immune system activation and sDPP4 concentration. Finally, we observed that acute viral infection induced a transient increase in sDPP4, which correlated with the expansion of antigen-specific CD8 T cell responses. Our study demonstrates that sDPP4 concentrations are determined by the frequency and activation state of lymphocyte populations. Insights from these studies will support the use of sDPP4 concentration as a biomarker for inflammatory and infectious diseases.
Topics: Animals; Biomarkers; Bodily Secretions; Dipeptidyl Peptidase 4; Disease Models, Animal; Hematopoiesis; Humans; Influenza A virus; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Orthomyxoviridae Infections; Severe Combined Immunodeficiency; Solubility; T-Lymphocytes; Transplantation Chimera
PubMed: 30251416
DOI: 10.1111/cei.13163 -
The Journal of Allergy and Clinical... Oct 2014I review how diverse inherited and acquired abnormalities in epidermal structural and enzymatic proteins converge to produce defective permeability barrier function and... (Review)
Review
I review how diverse inherited and acquired abnormalities in epidermal structural and enzymatic proteins converge to produce defective permeability barrier function and antimicrobial defense in patients with atopic dermatitis (AD). Although best known are mutations in filaggrin (FLG), mutations in other member of the fused S-100 family of proteins (ie, hornerin [hrn] and filaggrin 2 [flg-2]); the cornified envelope precursor (ie, SPRR3); mattrin, which is encoded by TMEM79 and regulates the assembly of lamellar bodies; SPINK5, which encodes the serine protease inhibitor lymphoepithelial Kazal-type trypsin inhibitor type 1; and the fatty acid transporter fatty acid transport protein 4 have all been linked to AD. Yet these abnormalities often only predispose to AD; additional acquired stressors that further compromise barrier function, such as psychological stress, low ambient humidity, or high-pH surfactants, often are required to trigger disease. T(H)2 cytokines can also compromise barrier function by downregulating expression of multiple epidermal structural proteins, lipid synthetic enzymes, and antimicrobial peptides. All of these inherited and acquired abnormalities converge on the lamellar body secretory system, producing abnormalities in lipid composition, secretion, and/or extracellular lamellar membrane organization, as well as antimicrobial defense. Finally, I briefly review therapeutic options that address this new pathogenic paradigm.
Topics: Animals; Bodily Secretions; Dermatitis, Atopic; Fatty Acid Transport Proteins; Filaggrin Proteins; Gene-Environment Interaction; Humans; Immunity, Innate; Inclusion Bodies; Intermediate Filament Proteins; Lipid Metabolism; Membrane Proteins; Proteinase Inhibitory Proteins, Secretory; Proteolysis; Serine Peptidase Inhibitor Kazal-Type 5; Skin
PubMed: 25131691
DOI: 10.1016/j.jaci.2014.05.048 -
International Journal of Molecular... Dec 2021Resolvin (Rv) D2 and RvD1 are biosynthesized from docosahexaenoic acid (DHA) and promote resolution of inflammation in multiple organs and tissues, including the...
Resolvin (Rv) D2 and RvD1 are biosynthesized from docosahexaenoic acid (DHA) and promote resolution of inflammation in multiple organs and tissues, including the conjunctiva. Histamine is a mediator produced by mast cells in the conjunctiva during the allergic response. We determined the interaction of RvD2 with histamine and its receptor subtypes in cultured conjunctival goblet cells and compared them with RvD1 by measuring intracellular [Ca] and mucous secretion. Treatment with RvD2 significantly blocked the histamine-induced [Ca] increase as well as secretion. RvD2 and RvD1 counter-regulate different histamine receptor subtypes. RvD2 inhibited the increase in [Ca] induced by the activation of H1, H3, or H4 receptors, whereas RvD1 inhibited H1 and H3 receptors. RvD2 and RvD1 also activate distinct receptor-specific protein kinases to counter-regulate the histamine receptors, probably by phosphorylation. Thus, our data suggest that the counter-regulation of H receptor subtypes by RvD2 and RvD1 to inhibit mucin secretion are separately regulated.
Topics: Animals; Bodily Secretions; Calcium; Cells, Cultured; Conjunctiva; Docosahexaenoic Acids; Female; Goblet Cells; Histamine; Humans; Male; Mucins; Protein Kinases; Rats; Rats, Sprague-Dawley
PubMed: 35008563
DOI: 10.3390/ijms23010141 -
Advances in Nutrition (Bethesda, Md.) Jan 2024Among exclusively breastfed infants, human milk (HM) provides complete nutrition in the first mo of life and remains an important energy source as long as breastfeeding...
Among exclusively breastfed infants, human milk (HM) provides complete nutrition in the first mo of life and remains an important energy source as long as breastfeeding continues. Consisting of digestible carbohydrates, proteins, and amino acids, as well as fats and fatty acids, macronutrients in human milk have been well studied; however, many aspects related to their relationship to growth in early life are still not well understood. We systematically searched Medline, EMBASE, the Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born healthy infants. From 9992 abstracts screened, 57 articles reporting observations from 5979 dyads were included and categorized based on their reporting of HM macronutrients and infant growth. There was substantial heterogeneity in anthropometric outcome measurement, milk collection timelines, and HM sampling strategies; thus, meta-analysis was not possible. In general, digestible carbohydrates were positively associated with infant weight outcomes. Protein was positively associated with infant length, but no associations were reported for infant weight. Finally, HM fat was not consistently associated with any infant growth metrics, though various associations were reported in single studies. Fatty acid intakes were generally positively associated with head circumference, except for docosahexaenoic acid. Our synthesis of the literature was limited by differences in milk collection strategies, heterogeneity in anthropometric outcomes and analytical methodologies, and by insufficient reporting of results. Moving forward, HM researchers should accurately record and account for breastfeeding exclusivity, use consistent sampling protocols that account for the temporal variation in HM macronutrients, and use reliable, sensitive, and accurate techniques for HM macronutrient analysis.
Topics: Child; Female; Humans; Infant; Body Composition; Breast Feeding; Carbohydrates; Fatty Acids; Milk, Human; Nutrients; Proteins
PubMed: 37981047
DOI: 10.1016/j.advnut.2023.100149 -
Acta Biochimica Et Biophysica Sinica Feb 2023As the essential tissue for sperm maturation and storage, the epididymis secretes a number of tissue-specific proteins to exert its functions. Among these proteins,...
As the essential tissue for sperm maturation and storage, the epididymis secretes a number of tissue-specific proteins to exert its functions. Among these proteins, epididymal lipocalins have been intensively studied because of their epididymis-specific expression pattern and clustered genomic organization. In this study, , a member of the rat epididymal lipocalin family, is identified and elaborately characterized. The cDNA sequence of consists of 719 nucleotides and encodes a 176 amino-acid protein with a predicted N-terminal signal peptide of 19 amino acids. shares a similar genomic structure and predicted 3D protein structure with other lipocalin family members. A recombinant rLCN13 mature peptide of 157 amino acids is expressed and purified, which is used to raise a polyclonal antibody against rLCN13 with high specificity and sensitivity. Northern blot, western blot, and immunohistochemistry assays reveal that is an epididymis-specific gene which is expressed predominantly in the initial segment and proximal caput epididymis and influenced by androgen. The rLCN13 protein is modified by N-glycosylation and secreted into the epididymal lumen, and then binds to the acrosome region of the sperm. Our data demonstrate that exhibits a specific temporospatial expression pattern and androgen dependence, indicating its potential roles in sperm maturation.
Topics: Rats; Male; Animals; Amino Acid Sequence; Lipocalins; Androgens; Epididymis; Semen; Spermatozoa; Recombinant Proteins
PubMed: 36762499
DOI: 10.3724/abbs.2023008 -
Fluids and Barriers of the CNS Mar 2022Cerebrospinal fluid (CSF) envelops the brain and fills the central ventricles. This fluid is continuously replenished by net fluid extraction from the vasculature by the... (Review)
Review
Cerebrospinal fluid (CSF) envelops the brain and fills the central ventricles. This fluid is continuously replenished by net fluid extraction from the vasculature by the secretory action of the choroid plexus epithelium residing in each of the four ventricles. We have known about these processes for more than a century, and yet the molecular mechanisms supporting this fluid secretion remain unresolved. The choroid plexus epithelium secretes its fluid in the absence of a trans-epithelial osmotic gradient, and, in addition, has an inherent ability to secrete CSF against an osmotic gradient. This paradoxical feature is shared with other 'leaky' epithelia. The assumptions underlying the classical standing gradient hypothesis await experimental support and appear to not suffice as an explanation of CSF secretion. Here, we suggest that the elusive local hyperosmotic compartment resides within the membrane transport proteins themselves. In this manner, the battery of plasma membrane transporters expressed in choroid plexus are proposed to sustain the choroidal CSF secretion independently of the prevailing bulk osmotic gradient.
Topics: Biological Transport; Choroid Plexus; Epithelium; Membrane Transport Proteins
PubMed: 35317823
DOI: 10.1186/s12987-022-00323-1 -
Scientific Reports Mar 2021Signal peptides and secretory carrier proteins are commonly used to secrete heterologous recombinant protein in Gram-negative bacteria. The Escherichia coli...
Signal peptides and secretory carrier proteins are commonly used to secrete heterologous recombinant protein in Gram-negative bacteria. The Escherichia coli osmotically-inducible protein Y (OsmY) is a carrier protein that secretes a target protein extracellularly, and we have previously applied it in the Bacterial Extracellular Protein Secretion System (BENNY) to accelerate directed evolution. In this study, we reported the first application of random and combinatorial mutagenesis on a carrier protein to enhance total secretory target protein production. After one round of random mutagenesis followed by combining the mutations found, OsmY(M3) (L6P, V43A, S154R, V191E) was identified as the best carrier protein. OsmY(M3) produced 3.1 ± 0.3 fold and 2.9 ± 0.8 fold more secretory Tfu0937 β-glucosidase than its wildtype counterpart in E. coli strains BL21(DE3) and C41(DE3), respectively. OsmY(M3) also produced more secretory Tfu0937 at different cultivation temperatures (37 °C, 30 °C and 25 °C) compared to the wildtype. Subcellular fractionation of the expressed protein confirmed the essential role of OsmY in protein secretion. Up to 80.8 ± 12.2% of total soluble protein was secreted after 15 h of cultivation. When fused to a red fluorescent protein or a lipase from Bacillus subtillis, OsmY(M3) also produced more secretory protein compared to the wildtype. In this study, OsmY(M3) variant improved the extracellular production of three proteins originating from diverse organisms and with diverse properties, clearly demonstrating its wide-ranging applications. The use of random and combinatorial mutagenesis on the carrier protein demonstrated in this work can also be further extended to evolve other signal peptides or carrier proteins for secretory protein production in E. coli.
Topics: Bacillus subtilis; Bacterial Secretion Systems; Escherichia coli; Escherichia coli Proteins; Lipase; Luminescent Proteins; Microorganisms, Genetically-Modified; Mutagenesis; Mutation Rate; Periplasmic Binding Proteins; Protein Sorting Signals; Protein Transport; Recombinant Fusion Proteins; Secretory Pathway; Temperature; Thermobifida; beta-Glucosidase; Red Fluorescent Protein
PubMed: 33674702
DOI: 10.1038/s41598-021-84859-6 -
Future Medicinal Chemistry Oct 2014
Topics: Animals; Chemistry, Pharmaceutical; Enzymes; Ion Channels; Membrane Transport Proteins; Peptides; Protein Binding; Receptors, G-Protein-Coupled; Venoms
PubMed: 25406000
DOI: 10.4155/fmc.14.117 -
Optometry and Vision Science : Official... Sep 2015Mucins are among the many important constituents of a healthy tear film. Mucins secreted and/or associated with conjunctival goblet cells, ocular mucosal epithelial... (Review)
Review
PURPOSE
Mucins are among the many important constituents of a healthy tear film. Mucins secreted and/or associated with conjunctival goblet cells, ocular mucosal epithelial cells, and the lacrimal gland must work together to create a stable tear film. Although many studies have explored the mechanism(s) whereby mucins maintain and protect the ocular surface, the effects of dry eye on the structure and function of ocular mucins are unclear. Here, we summarize current findings regarding ocular mucins and how they are altered in dry eye.
METHODS
We performed a literature review of studies exploring the expression of mucins produced and/or associated with tissues that comprise the lacrimal functional unit and how they are altered in dry eye. We also summarize new insights on the immune-mediated effects of aqueous tear deficiency on ocular surface mucins that we discovered using a mouse model of dry eye.
RESULTS
Although consistent decreases in MUC5AC and altered expression of membrane-bound mucins have been noted in both Sjögren and non-Sjögren dry eye, many reports of altered mucins in dry eye are contradictory. Mechanistic studies, including our own, suggest that changes in the glycosylation of mucins rather than the proteins themselves may occur as the direct result of local inflammation induced by proinflammatory mediators, such as interleukin-1.
CONCLUSIONS
Altered expression of ocular mucins in dry eye varies considerably from study to study, likely attributed to inherent difficulties in analyzing small-volume tear samples, as well as differences in tear collection methods and disease severity in dry eye cohorts. To better define the functional role of ocular mucin glycosylation in the pathogenesis of dry eye disease, we propose genomic and proteomic studies along with biological pathway analysis to reveal novel avenues for exploration.
Topics: Animals; Dry Eye Syndromes; Glycosylation; Humans; Membrane Glycoproteins; Mucins; Tears
PubMed: 26267059
DOI: 10.1097/OPX.0000000000000664