Tick saliva has pleiotropic properties that facilitate persistence of the arthropod upon the host. We now describe a feeding-inducible protein in Ixodes scapularis saliva, Salp15, that inhibits CD4(+) T cell activation. The mechanism involves the repression of calcium fluxes triggered by TCR ligation and results in lower production of interleukin-2. Salp15 also inhibits the development of CD4(+) T cell-mediated immune responses in vivo, demonstrating the functional importance of this protein. Salp15 provides a molecular basis for understanding the immunosuppressive activity of I. scapularis saliva and vector-host interactions.
Gingivo-buccal oral squamous cell carcinoma (OSCC-GB), an anatomical and clinical subtype of head and neck squamous cell carcinoma (HNSCC), is prevalent in regions where tobacco-chewing is common. Exome sequencing (n=50) and recurrence testing (n=60) reveals that some significantly and frequently altered genes are specific to OSCC-GB (USP9X, MLL4, ARID2, UNC13C and TRPM3), while some others are shared with HNSCC (for example, TP53, FAT1, CASP8, HRAS and NOTCH1). We also find new genes with recurrent amplifications (for example, DROSHA, YAP1) or homozygous deletions (for example, DDX3X) in OSCC-GB. We find a high proportion of C>G transversions among tobacco users with high numbers of mutations. Many pathways that are enriched for genomic alterations are specific to OSCC-GB. Our work reveals molecular subtypes with distinctive mutational profiles such as patients predominantly harbouring mutations in CASP8 with or without mutations in FAT1. Mean duration of disease-free survival is significantly elevated in some molecular subgroups. These findings open new avenues for biological characterization and exploration of therapies.
An immunological screening strategy was used to select microbial genes expressed only in the host.
Rabbits or guinea pigs infested with Ixodes scapularis acquire resistance to tick bites, a phenomenon, known as tick immunity, that is partially mediated by antibody. To determine the salivary gland antigens that elicit antibodies in the host, an I. scapularis salivary gland cDNA expression library was probed with serum from tick-immune rabbits. Sera from sensitized rabbits strongly recognized 47 of 100,000 library clones in an antibody-screening assay. These 47 clones encoded 14 different I. scapularis genes, including a glutathione peroxidase homologue. Expression of these 14 genes in engorged tick salivary glands was confirmed by reverse-transcription polymerase chain reaction. The I. scapularis glutathione peroxidase homologue, named salp25D, was expressed in both unfed and fed nymphal salivary glands. Recombinant Salp25D was able to catalyze the reduction of hydrogen peroxide in the presence of reduced glutathione and glutathione reductase. These results categorize the prominent salivary gland proteins in I. scapularis and demonstrate the presence of a potent antioxidant in tick saliva.
The temporal synthesis of the P21 protein of Borrelia burgdorferi and the development of the humoral response to this antigen was assessed in infected mice. p21 is a member of the ospE-F gene family and its protein, P21, has been shown to be expressed by B. burgdorferi within infected mice but not by spirochetes cultured in vitro. P21 was not detected on B. burgdorferi in unfed or engorged Ixodes dammini (also known as I. scapularis ) ticks, further supporting the postulate that P21 synthesis is specific for the mammalian host. In B. burgdorferi -infected mice, ospE mRNA and OspE antibodies were observed at 7 d, whereas p21 mRNA and P21-specific antibodies were detected at 21-28 d, suggesting that p21 is expressed later than ospE . Moreover, ospA mRNA was not discernible until day 14, indicating that ospA , like p21 , is not expressed in the early stages of tick-transmitted murine Lyme borreliosis. Because p21 is expressed during infection in mice, we assessed the human humoral response to P21. 28% (34 of 122) of the patients with either early-or late-stage Lyme disease, and 33% (11 of 33) of the individuals with Lyme arthritis had P21 antibodies, suggesting that a P21 response may serve, at least partially, as a marker of infection. Active immunization with recombinant P21 did not protect C3H mice from tick-borne B. burgdorferi infection, and passive transfer of P21 antiserum to infected mice did not alter the course of disease. These data suggest that the antigenic structure of B. burgdorferi changes during the early stages of murine infection. ( J. Clin. Invest. 1997. 99: 987-995.)
Phosphorus is the second most critical macronutrient after nitrogen required for metabolism, growth, and development of plants. Despite the abundance of phosphorus in both organic and inorganic forms in the soil, it is mostly unavailable for plant uptake due to its complexation with metal ions in the soil. The use of agrochemicals to satisfy the demand for phosphorus to improve crop yield has led to the deterioration of the ecosystem and soil health, as well as an imbalance in the soil microbiota. Consequently, there is a demand for an alternate cost-effective and eco-friendly strategy for the biofortification of phosphorus. One such strategy is the application of phosphate-solubilizing microorganisms which can solubilize insoluble phosphates in soil by different mechanisms like secretion of organic acids, enzyme production, and excretion of siderophores that can chelate the metal ions and form complexes, making phosphates available for plant uptake. These microbes not only solubilize phosphates but also promote plant growth and crop yield by producing plant-growth-promoting hormones like auxins, gibberellins, and cytokinins, antibiosis against pathogens, 1-aminocyclopropane-1-carboxylic acid deaminase which enhances plant growth under stress conditions, improving plant resistance to heavy metal toxicity, and so on. Pyrroloquinoline quinine (pqq) and glucose dehydrogenase (gcd) are the representative genes for phosphorus solubilization in microorganisms. The content presented in this review paper focuses on different mechanisms and modes of action of phosphate-solubilizing microorganisms, their contribution to phosphorus solubilization, growth-promoting attributes in plants, and the molecular aspects of phosphorus solubilization.
Abstract. We examined the effect of repeated infestation of guinea pigs with Ixodes scapularis on the capacity of ticks to transmit Borrelia burgdorferi infection. Repeated challenges with nymphs or larvae lead to a reduction in duration of nymphal tick attachment and weight of recovered ticks consistent with the development of tick immunity. Only one of 18 I. scapularis-immune guinea pigs challenged with B. burgdorferi-infected nymphal ticks became infected, whereas 10 of 18 naive guinea pigs similarly challenged became infected. We conclude that tick immunity interferes with borrelial transmission.Ticks are the most common vector transmitting diseases to humans in the United States. 1 The ixodids, also called hard-bodied ticks, have a complex life cycle involving egg, larval, nymphal, and adult stages. Development of the later three stages requires ingestion of blood. The prolonged period of feeding, 48-96 hr for larvae and nymphs, allows an immune response to develop in certain hosts against tick components. Trager first observed that repeated feeding of larvae or nymphs of Dermacentor sp. upon guinea pigs resulted in tick immunity. 2 Tick immunity is the capacity of previously exposed hosts to interfere with tick feeding and development. A reduction in tick weight, duration of attachment, number of ticks feeding, size of egg mass, and molting success are parameters to measure immunity. In addition to guinea pigs, tick immunity has been described in cattle and rabbits. [3][4][5][6][7] While some have reported anti-tick immunity in mice, 8 others have reported that it did not occur. 9 Wikel and others have recently reported that BALB/c mice repeatedly infested with pathogen-free Ixodes scapularis ticks failed to become infected when subsequently infested with Borrelia burgdorferi-infected ticks, even though mean weights of fed ticks and percentage reaching repletion did not indicate development of acquired resistance. 10 Development of tick immunity involves the interactions of tick antigens with host antibodies, T cells, B cells, mast cells, and basophils. 11 Langerhans' cells in the skin process and present tick antigens to lymphocytes that develop into sensitized lymphocytes and plasma cells secreting antibodies of various isotypes; among these are tissue-binding or homocytotropic antibodies. Antibodies bound to mast cells and basophils through their Fc receptors recognize tick antigens and induce degranulation resulting in development of microvesicles at the attachment site. Also contributing to the various manifestations of tick immunity are the multiple lymphokines, monokines, and chemokines released at the site of attachment. Basophil accumulation at tick attachment sites characterizes the immune reaction termed cutaneous basophil hypersensitivity, 12, 13 although the relative role of this reaction compared with the various other immunoreactants in producing the elements of tick immunity is not well defined, and may vary in different host species.The present paper evaluates the response of guinea pigs t...
Borrelia burgdorferi spirochetes that do not cause arthritis or carditis were developed and used to investigate Lyme disease pathogenesis. A clonal isolate of B. burgdorferi N40 (cN40), which induces disease in C3H/HeN (C3H) mice, was repeatedly passaged in vitro to generate nonpathogenic spirochetes. The passage 75 isolate (N40-75) was infectious for C3H mice but did not cause arthritis or carditis, and spirochetes were at low levels or absent in the joints or hearts, respectively. N40-75 could, however, cause disease in severe combined immunodeficient (SCID) mice, suggesting that the response in immunocompetent mice prevented effective spirochete dissemination and the subsequent development of arthritis and carditis. Administration of immune sera at 4 days after spirochete challenge aborted N40-75, but not cN40, infection in SCID mice. A B. burgdorferi genomic expression library was differentially probed with sera from cN40-and N40-75-infected mice, to identify genes that may not be effectively expressed by N40-75 in vivo. N40-75 was defective in the up-regulation of several genes that are preferentially expressed during mammalian infection, including dbpAB, bba64, and genes that map to the cp32 family of plasmids. These data suggest that adaptation and gene expression may be required for B. burgdorferi to effectively colonize the host, evade humoral responses, and cause disease.Borrelia burgdorferi, the causative agent of Lyme disease, is the most common vector-borne pathogen in the United States (15). B. burgdorferi-infected mice develop arthritis and carditis, thereby partially mimicking the human illness (3,5,8,10,19,43). The pathogenesis of murine Lyme borreliosis is multifactorial. The severity of disease has been associated with the number of B. burgdorferi in the affected organs (57), the virulence of specific spirochete isolates (12,32,40), and the host immune response to this organism (2,11,33,35,37,53,56). The severity of murine Lyme arthritis is genotype dependent. For example, C3H/HeN (C3H) mice develop more severe arthritis and have greater numbers of spirochetes in the joints than BALB/c mice (5,36,44).B. burgdorferi spirochetes adapt to different environments during their life cycle in Ixodes scapularis ticks and the reservoir host. Within engorging ticks, the B. burgdorferi protein expression dramatically changes, with the synthesis of OspC and down-regulation of OspA (21, 46). These changes are likely to occur in response to the incoming blood meal, temperature shifts, and alterations in spirochete density (21,42,49). In the mammalian host, B. burgdorferi must evade host antibodies that arise in response to infection, and selective gene expression and recombination events may facilitate spirochete survival (21, 58-60). Several genes, including eppA, ospE/F paralogues (erps), bbk32, bbk50, and the decorin-binding protein gene dbpA, are not expressed, or are expressed at low levels, by B. burgdorferi cultured in laboratory medium but are apparently up-regulated during infection (1,16,25,51,54)....
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